Abstract
Past, present, and future research into hepatic stellate cells (HSCs, also called vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells, or Ito cells) are summarized and discussed in this review. Kupffer discovered black-stained cells in the liver using the gold chloride method and named them stellate cells (Sternzellen in German) in 1876. Wake rediscovered the cells in 1971 using the same gold chloride method and various modern histological techniques including electron microscopy. Between their discovery and rediscovery, HSCs disappeared from the research history. Their identification, the establishment of cell isolation and culture methods, and the development of cellular and molecular biological techniques promoted HSC research after their rediscovery. In mammals, HSCs exist in the space between liver parenchymal cells (PCs) or hepatocytes and liver sinusoidal endothelial cells (LSECs) of the hepatic lobule, and store 50–80% of all vitamin A in the body as retinyl ester in lipid droplets in the cytoplasm. SCs also exist in extrahepatic organs such as pancreas, lung, and kidney. Hepatic (HSCs) and extrahepatic stellate cells (EHSCs) form the stellate cell (SC) system or SC family; the main storage site of vitamin A in the body is HSCs in the liver. In pathological conditions such as liver fibrosis, HSCs lose vitamin A, and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan, glycosaminoglycan, and adhesive glycoproteins. The morphology of these cells also changes from the star-shaped HSCs to that of fibroblasts or myofibroblasts.
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References
Adachi M, Brenner DA (2008) High molecular weight adiponectin inhibits proliferation of hepatic stellate cells via activation of adenosine monophosphate-activated protein kinase. Hepatology 47:677–685
Adachi M, Osawa Y, Uchinami H, Kitamura T, Accili D, Brenner DA (2007) The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells. Gastroenterology 132:1434–1446
Aimed Q, Hines JE, Harrison D, Burt AD (1991) Expression of muscle-associated cytoskeletal proteins by human sinusoidal liver cells. In: Wisse E, Knook DL, McCuskey RS (eds) Cells of the hepatic sinusoid, vol 3. Kupffer Cell Foundation, Leiden, pp 203–206
Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P (2015) Molecular biology of the cell, 6th edn. Garland Science, New York
Anan A, Baskin-Bey ES, Bronk SF, Werneburg NW, Shah VH, Gores GJ (2006) Proteasome inhibition induces hepatic stellate cell apoptosis. Hepatology 43:335–344
Andersen KB, Nilsson A, Blomhoff HK, Øyen TB, Gabrielsen OS, Norum KR, Blomhoff R (1992) Direct mobilization of retinol from hepatic perisinusoidal stellate cells to plasma. J Biol Chem 267:1340–1344
Andrade CMB, Trindade VMT, Cardoso CCA, Ziulkoski AL, Trugo LC, Guaragna RM, Borojevic R, Guma FCR (2003) Changes of sphingolipid species in the phenotype conversion from myofibroblasts to lipocytes in hepatic stellate cells. J Cell Biochem 88:533–544
Ankoma-Sey V, Wang Y, Dai Z (2000) Hypoxic stimulation of vascular endothelial growth factor expression in activated rat hepatic stellate cell. Hepatology 31:141–148
Antoine M, Wirz W, Tag CG, Gressner AM, Marvituna M, Wycislo M, Hellerbrand C, Kiefer P (2007) Expression and function of fibroblast growth factor (FGF) 9 in hepatic stellate cells and its role in toxic liver injury. Biochem Biophys Res Commun 361:335–341
Apte MV, Haber PS, Applegate TL, Norton ID, McCaughan GW, Korsten MA, Pirola RC, Wilson JS (1998) Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut 43:128–133
Apte MV, Haber PS, Darby SJ, Rodgers SC, McCaughan GW, Korsten MA, Pirola RC, Wilson JS (1999) Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis. Gut 44:534–541
Arber N, Zajicek G, Ariel I (1988) The streaming liver II. Hepatocyte life history. Liver 8:80–87
Arber N, Zajicek G, Shamir R, Kenet G, Raanani P, Nordenberg J, Sidi Y (1992) Bromobenzene accelerates hepatocyte streaming in rats. Hepatology 103:1273–1276
Armendariz-Borunda J, Greenwel P, Rojkind M (1989) Kupffer cells from CCl4-treated rat livers induce skin fibroblast and liver fat-storing cell proliferation in culture. Matrix 9:150–158
Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM (1987) Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237:268–275
Arthur MJP (2000) Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 279:G245–G249
Arthur MJP (2002) Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology 122:1525–1528
Asahina K, Zhou B, Pu WT, Tsukamoto H (2011) Septum transversum-derived mesothelium gives rise to hepatic stellate cells and perivascular mesenchymal cells in developing mouse liver. Hepatology 53:983–995
Athari A, Hänecke K, Jungermann K (1994) Prostaglandin F2 and D2 release from primary Ito cell cultures after stimulation with noradrenaline and ATP but not adenosine. Hepatology 20:142–148
Baba S, Fujii H, Hirose T, Yasuchika K, Azuma H, Hoppo T, Naito M, Machimoto T, Ikai I (2004) Commitment of bone marrow cells to hepatic stellate cells in mouse. J Hepatol 40:255–260
Bachem MG, Riess U, Melchior R, Sell K-M, Gressner AM (1989) Transforming growth factors (TGFa and TGFb1) stimulate chondroitin sulfate and hyaluronate synthesis in cultured rat liver fat storing cells. FEBS Lett 257:134–137
Bachem MG, Schneider E, Groß H, Weidenbach H, Schmid RM, Menke A, Siech M, Beger H, Grünert A, Adler G (1998) Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology 115:421–432
Bahr MJ, Vincent KJ, Arthur MJP, Fowler AV, Smart DE, Wright MC, Clark IM, Benyon RC, Iredale JP, Mann DA (1999) Control of the tissue inhibitor of metalloproteinases-1 promoter in culture-activated rat hepatic stellate cells: regulation by activator protein-1 DNA binding proteins. Hepatology 29:839–848
Balabaud C, Bioulac-Sage P, Desmoulière A (2004) The role of hepatic stellate cells in liver regeneration. J Hepatol 40:1023–1026
Ballardini G, Groff P, de Glorgi LB, Schuppan D, Bianchi FB (1994) Ito cell heterogeneity: desmin negative Ito cells in normal rat liver. Hepatology 19:440–446
Balmer JE, Blomhoff R (2002) Gene expression regulation by retinoic acid. J Lipid Res 43:1773–1808
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252
Barrie LA, Gregor D, Hargrave B, Lake R, Muir D, Shearer R, Tracey B, Bidleman T (1992) Arctic contaminants: sources, occurrence and pathways. Sci Total Environ 122:1–74
Bastien J, Rochette-Egly C (2004) Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene 328:1–16
Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115:209–218
Bataller R, Paik Y-H, Lindquist JH, Lemasters JJ, Brenner DA (2004) Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells. Gastroenterology 126:529–540
Batten ML, Imanishi Y, Maeda T, Tu DC, Moise AR, Bronson D, Possin D, Van Gelder RN, Baehr W, Palczewski K (2004) Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver. J Biol Chem 279:10422–10432
Bauer M, Schuppan D (2001) TGFb1 in liver fibrosis: time to change paradigms? FEBS Lett 502:1–3
Båvik CO, Eriksson U, Allen RA, Peterson PA (1991) Identification and partial characterization of a retinal pigment epithelial membrane receptor for plasma retinol-binding protein. J Biol Chem 266:14978–14985
Båvik CO, Busch C, Eriksson U (1992) Characterization of a plasma retinol-binding protein membrane receptor expressed in the retinal pigment epithelium. J Biol Chem 267:23035–23042
Båvik CO, Levy F, Hellman U, Wernstedt C, Eriksson U (1993) The retinal pigment epithelial membrane receptor for plasma retinol-binding protein. J Biol Chem 268:20540–20546
Beno DWA, Rapp UR, Davis BH (1994) Prostaglandin E suppression of platelet-derived-growth-factor-induced Ito cell mitogenesis occurs independent of raf perinuclear translocation and nuclear proto-oncogene expression. Biochim Biophys Acta Mol Cell Res 1222:292–300
Benyon RC, Arthur MJP (2001) Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 21:373–384
Benyon RC, Iredale JP (2000) Is liver fibrosis reversible? Gut 46:443–446
Berkley HJ (1893) Studies in the histology of the liver. III. The perivascular cell of the rabbits liver. Anat Anz 8:787–792
Biesalski HK, Frank J, Beck SC, Heinrich F, Illek B, Reifen R, Gollnick H, Seeliger MW, Wissinger B, Zrenner E (1999) Biochemical but not clinical vitamin A deficiency results from mutations in the gene for retinol binding protein. Am J Clin Nutr 69:931–936
Bioulac-Sage P, Lafon ME, Saric J, Balabaud C (1990) Nerves and perisinusoidal cells in human liver. J Hepatol 10:105–112
Blanchette-Mackie EJ, Dwyer NK, Barber T, Coxey RA, Takeda T, Rondinone CM, Theodorakis JL, Greenberg AS, Londos C (1995) Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes. J Lipid Res 36:1211–1226
Blaner WS (1989) Retinol-binding protein: the serum transport protein for vitamin A. Endocr Rev 10:308–316
Blaner WS (2007) STRA6, a cell-surface receptor for retinol-binding protein: the plot thickens. Cell Metab 5:164–166
Blaner WS, Hendriks HF, Brouwer A, de Leeuw AM, Knook DL, Goodman DS (1985) Retinoids, retinoid-binding proteins, and retinyl palmitate hydrolase distributions in different types of rat liver cells. J Lipid Res 26:1241–1251
Blaner WS, Dixon JL, Moriwaki H, Martino RA, Stein O, Stein Y, Goodman DS (1987) Studies on the in vivo transfer of retinoids from parenchymal to stellate cells in rat liver. Eur J Biochem 164:301–307
Blaner WS, van Bennekum AM, Brouwer A, Hendriks HFJ (1990) Distribution of lecithin-retinol acyltransferase activity in different types of rat liver cells and subcellular fractions. FEBS Lett 274:89–92
Blaner WS, O’Byrne SM, Wongsiriroj N, Kluwe J, D’Ambrosio DM, Jiang H, Schwabe RF, Hillman EMC, Piantedosi R, Libien J (2009) Hepatic stellate cell lipid droplets: a specialized lipid droplet for retinoid storage. Biochim Biophys Acta Mol Cell Biol Lipids 1791:467–473
Block GD, Locker J, Bowen WC, Peterson BE, Katyal S, Strom SC, Riley T, Howard TA, Michalopoulos GK (1996) Population expansion, clonal division, and specific differentiation patterns in primary cultures of hepatocytes by HGF/SF, EGF, and TGFα in a chemically defined (HGM) medium. J Cell Biol 132:1133–1149
Blomhoff R (1987) Hepatic retinol metabolism: role of the various cell types. Nutr Rev 45:257–263
Blomhoff R (1994) Vitamin A in health and disease. Marcel Dekker, New York
Blomhoff R, Berg T (1990) Isolation and cultivation of rat liver stellate cells. Methods Enzymol 190:58–71
Blomhoff R, Blomhoff HK (2006) Overview of retinoid metabolism and function. J Neurobiol 66:606–630
Blomhoff R, Wake K (1991) Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. FASEB J 5:271–277
Blomhoff R, Helgerud P, Rasmussen M, Berg T, Norum KR (1982) In vivo uptake of chylomicron [3H]retinyl ester by rat liver: evidence for retinol transfer from parenchymal to nonparenchymal cells. Proc Natl Acad Sci USA 79:7326–7330
Blomhoff R, Holte K, Naess L, Berg T (1984a) Newly administered [3H]retinol is transferred from hepatocytes to stellate cells in liver for storage. Exp Cell Res 150:186–193
Blomhoff R, Smedsrød B, Eskild W, Granum PE, Berg T (1984b) Preparation of isolated liver endothelial cells and Kupffer cells in high yield by means of an enterotoxin. Exp Cell Res 150:194–204
Blomhoff R, Norum KR, Berg T (1985a) Hepatic uptake of [3H]retinol bound to the serum retinol binding protein involves both parenchymal and perisinusoidal stellate cells. J Biol Chem 260:13571–13575
Blomhoff R, Rasmussen M, Nilsson A, Norum KR, Berg T, Blaner WS, Kato M, Mertz JR, Goodman DS, Eriksson U (1985b) Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells. J Biol Chem 260:13560–13565
Blomhoff R, Berg T, Norum KR (1988a) Newly administered [3H]retinol is transferred from hepatocytes to stellate cells in liver for storage. Exp Cell Res 150:186–193
Blomhoff R, Berg T, Norum KR (1988b) Distribution of retinol in rat liver cells: effect of age, sex and nutritional status. Br J Nutr 60:233–239
Blomhoff R, Berg T, Norum KR (1988c) Transfer of retinol from parenchymal to stellate cells in liver is mediated by retinol-binding protein. Proc Natl Acad Sci USA 85:3455–3458
Blomhoff R, Green MH, Berg T, Norum KR (1990) Transport and storage of vitamin A. Science 250:399–404
Blomhoff R, Green MH, Green JB, Berg T, Norum KR (1991) Vitamin A metabolism: new perspectives on absorption, transport, and storage. Physiol Rev 71:951–990
Blomhoff R, Green MH, Norum KR (1992a) Vitamin A: physiological and biochemical processing. Annu Rev Nutr 12:37–57
Blomhoff R, Senoo H, Smeland S, Bjerknes T, Norum KR (1992b) Cellular uptake of vitamin A. J Nutr Sci Vitam 38:327–330
Bloom W, Fawcett DW (1994) A textbook of histology, 12th edn. Chapman and Hall, New York
Blüher M, Tönjes A, Stumvoll M (2008) Does retinol-binding protein 4 cause or reflect fatty liver disease? Hepatology 48:4–6
Bonis PAL, Friedman SL, Kaplan MM (2001) Is liver fibrosis reversible? New Engl J Med 344:452–454
Braet F, Luo D, Spector I, Vermijlen D, Wisse E (2001) Endothelial and pit cells. In: Arias IM, Boyer JL, Chisari FV, Fausto N, Schachter D, Shafritz DA (eds) The liver: biology and pathobiology, 4th edn. Lippincott Williams and Wilkins, Philadelphia, pp 437–453
Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C (1997) Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein. J Lipid Res 38:2249–2263
Bronfenmajer S, Schaffner F, Popper H (1966) Fat-storing cells (lipocytes) in human liver. Arch Pathol 82:447–453
Brouwer A, Barelds RJ, de Leeuw AM, Blauw E, Plas A, Yap SH, van den Broek AMWC, Knook DL (1988a) Isolation and culture of Kupffer cells from human liver. Ultrastructure, endocytosis and prostaglandin synthesis. J Hepatol 6:36–49
Brouwer A, Wisse E, Knook DL (1988b) Sinusoidal endothelial cells and perisinusoidal fat-storing cells. In: Arias IM, Jakoby WB, Popper H, Schachter D, Sgfritz DA (eds) The liver: biology and pathobiology, 2nd edn. Raven, New York, pp 665–682
Browicz T (1900) Ueber intravasculaere Zellen in den Blutcapillaren der Lberacini. Arch Mikr Anat 55:420–426
Brown DA (2001) Lipid droplets: proteins floating on a pool of fat. Curr Biol 11:R446–R449
Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A (1994) Circulating fibrocytes define a new leucocyte subpopulation that mediate tissue repair. Mol Med 1:71–81
Buniatian G, Gebhardt R, Schrenk D, Hamprecht B (1996) Colocalization of three types of intermediate filament proteins in perisinusoidal stellate cells: glial fibrillary acidic protein as a new cellular marker. Eur J Cell Biol 70:23–32
Burgess HA, Daugherty LE, Thatcher TH, Lakatos HF, Ray DFM, Redonett M, Phipps RP, Sime PJ (2005) PPARγ agonists inhibit TGF-β induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol Lung Cell Mol Physiol 288:L1146–L1153
Calvo M, Tebar F, Lopez-Iglesias I, Enrich C (2001) Morphologic and functional characterization of caveolae in rat liver hepatocytes. Hepatology 33:1259–1269
Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ (2003) Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest 83:655–663
Carloni V, Ramanelli RG, Pinzani M, Laffi G, Gentilini P (1996) Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells. Gastroenterology 110:1127–1136
Carlson BM (1999) Human embryology and developmental biology, 2nd edn. Mosby, St. Louis
Cases S, Smith SJ, Zheng YW, Myers HM, Lear SR, Sande E, Novak S, Collins C, Welch CB, Lusis AJ, Erickson SK, Farese RV Jr (1998) Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc Natl Acad Sci USA 95:13018–13023
Casini A, Ceni E, Salzano R, Schuppan D, Milani S, Pellegrini G, Surrenti C (1994) Regulation of undulin synthesis and gene expression in human fat-storing cells by acetaldehyde and transforming growth factor-b1: comparison with fibronectin. Biochem Biophys Res Commun 199:1019–1026
Cassiman D, Roskams T (2002) Beauty is in the eye of the beholder: emerging concepts and pitfalls in hepatic stellate cell research. J Hepatol 37:527–535
Cassiman D, van Pelt J, De Vos R, Van Lommel F, Desmet V, Yap S-H, Roskams T (1999) Synaptophysin: a novel marker for human and rat hepatic stellate cells. Am J Pathol 155:1831–1839
Cassiman D, Denef C, Desmet VJ, Roskams T (2001a) Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors. Hepatology 33:148–158
Cassiman D, Roskams T, van Pelt J, Libbrecht L, Aertsen P, Crabbé T, Vankelecom H, Denef C (2001b) Alpha B-crystallin expression in human and rat hepatic stellate cells. J Hepatol 35:200–207
Cassiman D, Libbrecht L, Desmet V, Denef C, Roskams T (2002) Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers. J Hepatol 36:200–209
Cassiman D, Barlow A, Borght SV, Libbrecht L, Pachnis V (2006) Hepatic stellate cells do not derive from the neural crest. J Hepatol 44:1098–1104
Chang CS, Kokontis J, Liao ST (1988) Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 240:324–326
Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ (2001) Nuclear receptors and lipid physiology: opening the X-files. Science 294:1866–1870
Chen A, Davis BH (2000) The DNA binding protein BTEB mediates acetaldehyde-induced, jun N-terminal kinase-dependent α (I) collagen gene expression in rat hepatic stellate cells. Mol Cell Biol 20:2818–2826
Chen PS, Zhai WR, Zhou XM, Zhang JS, Zhang YE, Ling YQ, Gu YH (2001) Effects of hypoxia, hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 in hepatic stellate cells. World J Gastroenterol 7:647–651
Chen C, Zhang J, Li J, Huang J, Yang C, Huang G, Shi J (2004) Hydrodynamic-based in vivo transfection of retinoic X receptor-α gene can enhance vitamin A-induced attenuation of liver fibrosis in mice. Liver Int 24:679–686
Chiang JY (2002) Bile acid regulation of gene expression: roles of nuclear hormone receptors. Endocr Rev 23:443–463
Cho YM, Youn B-S, Lee H, Lee N, Min S-S, Kwak SH, Lee HK, Park KS (2006) Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes. Diabetes Care 29:2457–2461
Choi SH, Lee YJ, Park YJ, Kim KW, Lee EJ, Lim S, Park DJ, Kim SE, Park KS, Jang HC, Cho BY (2008) Retinol binding protein-4 elevation is associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance. J Clin Endocr Metab 93:2313–2318
Chytil F (1992) The lungs and vitamin A. Am J Physiol Lung Cell Mol Physiol 262:L517–L527
Clark EA, Brugge JS (1995) Integrins and signal transduction pathways: the road taken. Science 268:1995
Clement B, Grimaud JA, Campion JP, Deugnier Y, Guillouzo A (1986) Cell type involved in collagen and fibronectin production in normal and fibrotic human liver. Hepatology 6:225–234
Cogger VC, Warren A, Fraser R, Ngu M, McLean AJ, Le Couteur DG (2003) Hepatic sinusoidal pseudocapillarization with aging in the non-human primate. Exp Gerontol 38:1101–1107
Collardeau-Frachon S, Scoazec J-Y (2008) Vascular development and differentiation during human liver organogenesis. Anat Rec 291:614–627
Conneely OM, Sullivan WP, Toft DO, Birnbaumer M, Cook RG, Maxwell BL, Zarucki-Schulz T, Greene GL, Schrader WT, O’Malley BW (1986) Molecular cloning of the chicken progesterone receptor. Science 233:767–770
Corpechot C, Barbu V, Wendum D, Kinnman N, Rey C, Poupon R, Housset C, Rosmorduc O (2002) Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 35:1010–1021
Critchley DR (2000) Focal adhesions-the cytoskeletal connection. Curr Opin Cell Biol 12:133–139
Cukierman E, Pankov R, Stevens DR, Yamada KM (2001) Taking cell-matrix adhesion to the third dimension. Science 294:1708–1712
Da Silva Morais A, Abarca-Quinones J, Horsmans Y, Starkel P, Leclercq IA (2007) Peroxisome proliferated-activated receptor γ ligand, Pioglitazone, does not prevent hepatic fibrosis in mice. Int J Mol Med 19:105–112
Dack CL, Day CO, Johnson SJ, Burt AD (1997) Population kinetics of GFAP-positive cells following experimental acute liver injury. In: Wisse E, Knook DL, Balabaud C (eds) Cells of the hepatic sinusoid, vol 6. Kupffer Cell Foundation, Leiden, pp 59–61
Davis BH (1988) Transforming growth factor β responsiveness is modulated by extracellular collagen matrix during hepatic Ito cell culture. J Cell Physiol 136:547–553
Davis BH, Vucic A (1988) The effect of retinol on Ito cell proliferation in vitro. Hepatology 8:788–793
Davis BH, Vucic A (1989) Modulation of vitamin A metabolism during hepatic and intestinal culture. Biochem Biophys Acta 1010:318–324
Davis BH, Pratt BM, Madri JA (1987) Retinol and extracellular collagen matrices modulate hepatic Ito cell collagen phenotype and cellular retinol binding protein levels. J Biol Chem 262:10280–10286
Davis BH, Chen A, Beno DWA (1996) Raf and mitogen-activated protein kinase regulate stellate cell collagen gene expression. J Biol Chem 271:11039–11042
de Leeuw AM, Barelds RJ, de Zanger R, Knook DL (1982) Primary culture of endothelial cells of the rat liver. A model for ultrastructural and functional studies. Cell Tissue Res 223:201–215
de Leeuw AM, McCarthy SP, Geerts A, Knook DL (1984) Purified rat liver fat-storing cells in culture divide and contain collagen. Hepatology 4:392–403
De Minicis S, Brenner DA (2007) NOX in liver fibrosis. Arch Biochem Biophys 462:266–272
De Minicis S, Seki E, Uchinami H, Kluwe J, Zhang Y, Brenner DA, Schwabe R (2007) Gene expression profiles during hepatic stellate cell activation in culture and in vivo. Gastroenterology 132:1937–1946
Desmoulière A (2007) Hepatic stellate cells: the only cells involved in liver fibrogenesis? A dogma challenged. Gastroenterology 132:2059–2062
Desmoulière A, Xu G, Costa AMA, Yousef IM, Gabbiani G, Tuchweber B (1999) Effect of pentoxifylline on early proliferation and phenotypic modulation of fibrogenic cells in two rat models of liver fibrosis and on cultured hepatic stellate cells. J Hepatol 30:621–631
Desmoulière A, Darby IA, Gabbiani G (2003) Normal and pathologic soft tissue remodeling: role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab Invest 83:1689–1707
Dewailly E, Nantel A, Weber J-P, Meyer F (1989) High levels of PCBs in breast milk of Inuit women from arctic Quebec. Bull Environ Contam Toxicol 43:641–646
Dirami G, Massaro GD, Clerch LB, Ryan US, Reczek PR, Massaro D (2004) Lung retinol storing cells synthesize and secrete retinoic acid, an inducer of alveolus formation. Am J Physiol Cell Mol Physiol 286:L249–L256
Dong D, Ruuska SE, Levinthal DJ, Noy N (1999) Distinct roles for cellular retinoic acid-binding proteins I and II in regulating signaling by retinoic acid. J Biol Chem 274:23695–23698
Dooley S, Hamzavi J, Breitkopf K, Wiercinska E, Said HM, Lorenzen J, Dijke PT, Gressner AM (2003) Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats. Gastroenterology 125:178–191
Drummond JC, Bell ME (1935) Observation of the absorption of carotene and vitamin A. Br Med J 1:1208–1210
Du Bois AM (1968) The embryonic liver. In: Rouiller CH (ed) The liver, vol 1. Academic, New York, pp 1–39
Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, Wu S, Lang R, Iredale JP (2005) Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 115:56–65
During A, Harrison EH (2007) Mechanisms of provitamin A (carotenoid) and vitamin A (retinol) transport into and out of intestinal Caco-2 cells. J Lipid Res 48:2283–2294
Elias H (1955) Origin and early development of the liver in various vertebrates. Acta Hepatol 3:1–56
Elices MJ, Hemler ME (1989) The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others. Proc Natl Acad Sci USA 86:9906–9910
Elsharkawy AM, Wright MC, Hay RT, Arthur MJ, Hughes T, Bahr MJ, Degitz K, Mann DA (1999) Persistent activation of nuclear factor-B in cultured rat hepatic stellate cells involves the induction of potentially novel rel-like factors and prolonged changes in the expression of IB family proteins. Hepatology 30:761–769
Emsley J, Knight CG, Farndale RW, Barnes MJ, Liddington RC (2000) Structural basis of collagen recognition by integrin α2β1. Cell 101:47–56
Enzan H, Himeno H, Iwamura S, Onishi S, Saibara T, Yamamoto Y, Hara H (1994a) α-Smooth muscle actin-positive perisinusoidal stromal cells in human hepatocellular carcinoma. Hepatology 19:895–903
Enzan H, Himeno H, Iwamura S, Saibara T, Onishi S, Yamamoto Y, Hara H (1994b) Immunohistochemical identification of Ito cells and their myofibroblastic transformation in adult human liver. Virchows Arch 424:249–256
Enzan H, Himeno H, Hiroi M, Kiyoku H, Saibara T, Onishi S (1997) Development of hepatic sinusoidal structure with special reference to the Ito cells. Microsc Res Tech 39:336–349
Erickson N, Mohanty SK, Shivakumar P, Sabla G, Chakraborty R, Bezerra JA (2008) Temporal-spatial activation of apoptosis and epithelial injury in murine experimental biliary atresia. Hepatology 47:1567–1577
Eriksson U, Das K, Busch C, Nordlinder H, Rask L, Sundelin J, Sallstrom J, Peterson PA (1984) Cellular retinol-binding protein. Quantitation and distribution. J Biol Chem 259:13464–13470
Everett L, Galli A, Crabb D (2000) The role of hepatic peroxisome proliferator-activated receptors (PPARs) in health and disease. Liver 20:191–199
Fallowfield JA, Iredale JP (2003) Reversal of liver fibrosis and cirrhosis—an emerging reality. Scott Med J 49:3–6
Fawcett DW (1986) Bloom and Fawcett: a textbook of histology, 11th edn. W. B. Saunders, Philadelphia
Febbraio M, Hajjar DP, Silverstein RL (2001) CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest 108:785–791
Fennekohl A, Schieferdecker HL, Jungermann K, Püschel GP (1999) Differential expression of prostanoid receptors in hepatocytes, Kupffer cells, sinusoidal endothelial cells and stellate cells of rat liver. J Hepatol 30:38–47
Fimmel CJ, Brown KE, O’Neill R, Kladney RD (1996) Complement C4 protein expression by rat hepatic stellate cells. J Immunol 157:2601–2609
Fiorucci S, Antonelli E, Distrutti E, Severino B, Fiorentina R, Baldoni M, Caliendo G, Santagada V, Morelli A, Cirino G (2004a) PAR1 antagonism protects against experimental liver fibrosis. Role of proteinase receptors in stellate cell activation. Hepatology 39:365–375
Fiorucci S, Antonelli E, Rizzo G, Renga B, Mencarelli A, Riccardi L, Orlandi S, Pellicciari R, Morelli A (2004b) The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis. Gastroenterology 127:1497–1512
Fiorucci S, Rizzo G, Antonelli E, Renga B, Mencarelli A, Riccardi L, Morelli A, Pruzanski M, Pellicciari R (2005a) Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor γ contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis. J Pharmacol Exp Ther 315:58–68
Fiorucci S, Rizzo G, Antonelli E, Renga B, Mencarelli A, Riccardi L, Orlandi S, Pruzanski M, Morelli A, Pellicciari R (2005b) A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis. J Pharmacol Exp Ther 314:584–595
Fischer R, Cariers A, Reinehr R, Håussinger D (2002) Caspase 9-dependent killing of hepatic stellate cells by activated Kupffer cells. Gastroenterology 123:845–861
Fischer R, Reinehr R, Lu TP, Schönicke A, Warskulat U, Dienes HP, Häussinger D (2005) Intercellular communication via gap junctions in activated rat hepatic stellate cells. Gastroenterology 128:433–448
Fortuna VA, Trugo LC, Borojevic R (2001) Acyl-CoA:retinol acyltransferase (ARAT) and lecithin:retinol acyltransferase (LRAT) activation during the lipocyte phenotype induction in hepatic stellate cells. J Nutr Biochem 12:610–621
Friedamn SL, Arthur MJP (1989) Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. J Clin Invest 84:1780–1785
Friedman SL (1993) The cellular basis of hepatic fibrosis–Mechanisms and treatment strategies. New Engl J Med 328:1828–1835
Friedman SL (2000) Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 275:2247–2250
Friedman SL (2003) Liver fibrosis—from bench to bedside. J Hepatol 38:S38–S53
Friedman SL (2004) Stellate cells: a moving target in hepatic fibrogenesis. Hepatology 40:1041–1043
Friedman SL (2006) Transcriptional regulation of stellate cell activation. J Gastroenterol Hepatol 21:S79–S83
Friedman SL (2008a) Mechanisms of hepatic fibrogenesis. Gastroenterology 134:1655–1669
Friedman SL (2008b) Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 88:125–172
Friedman SL, Arthur MJP (2002) Reversing hepatic fibrosis. Sci Med 8:194–205
Friedman SL, Bansal MB (2006) Reversal of hepatic fibrosis—fact or fantasy? Hepatology 43:S82–S88
Friedman SL, Roll FJ, Boyles J, Bissell DM (1985) Hepatic lipocytes: the principal collagen-producing cells of normal rat liver. Proc Natl Acad Sci USA 82:8681–8685
Friedman SL, Roll FJ, Boyles J, Arenson DM, Bissell DM (1989a) Maintenance of differentiated phenotype of cultured rat hepatic lipocytes by basement membrane matrix. J Biol Chem 264:10756–10762
Friedman SL, Roll FJ, Bissell DM (1989b) Autocrine regulation of lipocyte matrix production: activation by extracellular matrix. In: Wisse E, Knook DL, Decker K (eds) Cells of the hepatic sinusoid, vol 2. Kupffer Cell Foundation, Rijswijk, pp 61–63
Friedman SL, Rockey DC, McGuire RF, Maher JJ, Boyles JK, Yamasaki G (1992) Isolated hepatic lipocytes and Kupffer cells from normal human liver: morphological and functional characteristics in primary culture. Hepatology 15:234
Friedman SL, Wei S, Blaner WS (1993) Retinol release by activated rat hepatic lipocytes: regulation by Kupffer cell-conditioned medium and PDGF. Am J Physiol Gastrointest Liver Physiol 264:G947–G952
Fuja TJ, Prost-Fuja MN, Titze IR (2005) Transdifferentiation of vocal-fold stellate cells and all-trans retinol-induced deactivation. Cell Tissue Res 322:417–424
Fuja TJ, Probst-Fuja MN, Titze IR (2006) Changes in expression of extracellular matrix genes, fibrogenic factors, and actin cytoskeletal organization in retinol treated and untreated vocal fold stellate cells. Matrix Biol 25:59–67
Fujimoto T, Ohsaki Y (2006) Cytoplasmic lipid droplets: rediscovery of an old structure as a unique platform. Ann NY Acad Sci 1086:104–115
Fujimoto T, Ohsaki Y, Cheng J, Suzuki M, Shinohara Y (2008) Lipid droplets: a classic organelle with new outfits. Histochem Cell Biol 130:263–279
Fujisawa G, Muto S, Okada K, Kusano E, Ishibashi S (2006) Mineralocorticoid receptor antagonist spironolactone prevents pig serum-induced hepatic fibrosis in rats. Transl Res 148:149–156
Fukuda-Taira S (1981) Hepatic induction in the avian embryo: specificity of reactive endoderm and inductive mesoderm. J Embryol Exp Morphol 63:111–125
Fukushima M, Enjoji M, Kohjima M, Sugimoto R, Ohta S, Kotoh K, Kuniyoshi M, Kobayashi K, Imamura M, Inoguchi T, Nakamuta M, Nawata H (2005) Adipose differentiation related protein induces lipid accumulation and lipid droplet formation in hepatic stellate cells. In Vitro Cell Dev Biol Anim 41:321–324
Gäbele E, Reif S, Tsukada S, Bataller R, Yata Y, Morris T, Schrum LW, Brenner DA, Rippe RA (2005) The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation. J Biol Chem 280:13374–13382
Galli A, Crabb D, Price D, Ceni E, Salzano R, Surrenti C, Casini A (2000) Peroxisome proliferator-activated receptor γ transcriptional regulation is involved in platelet-derived growth factor-induced proliferation of human hepatic stellate cells. Hepatology 31:101–108
Galli A, Crabb DW, Ceni E, Salzano R, Mello T, Svegliati-Baroni G, Ridolfi F, Trozzi L, Surrenti C, Casini A (2002) Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. Gastroenterology 122:1924–1940
Gallois C, Habib A, Tao J, Moulin S, Maclouf J, Mallat A, Lotersztajn S (1998) Role of NFκB in the antiproliferative effect of endothelin-1 and tumor necrosis factor-α in human hepatic stellate cells. J Biol Chem 273:23183–23190
Gao JG, Simon M (2006) Molecular screening for GS2 lipase regulators: inhibition of keratinocyte retinylester hydrolysis by TIP47. J Invest Dermatol 126:2087–2095
Gard AL, White FP, Dutton GR (1985) Extra-neural glial fibrillary acidic protein (GFAP) immunoreactivity in perisinusoidal stellate cells of rat liver. J Neuroimmunol 8:359–375
Gascon-Barre M, Demers C, Mirshahi A, Neron S, Zalzal S, Nanci A (2003) The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells. Hepatology 37:1034–1042
Geerts A (2004) On the origin of stellate cells: mesodermal, endodermal or neuro-ectodermal? J Hepatol 40:331–334
Geerts A, Geuze HJ, Slot JW, Voss B, Schuppan D, Schellinck P, Wisse E (1986) Immunogold localization of procollagen III, fibronectin and heparan sulfate proteoglycan on ultrathin frozen sections of the normal rat liver. Histochemistry 84:355–362
Geerts A, Bouwens L, Wisse E (1990a) Ultrastructure and function of hepatic fat-storing and pit cells. J Electron Microsc Tech 14:247–256
Geerts A, Schuppan D, Lazeroms S, De Zanger R, Wisse E (1990b) Collagen type I and III occur together in hybrid fibrils in the space of Disse of normal rat liver. Hepatology 12:233–241
Geerts A, Bleser PD, Hautekeete ML, Niki T, Wisse E (1994) Fat-storing (Ito) cell biology. In: Arias IA, Boyer JL, Fausto N, Jakoby WB, Schachter DA, Shafritz DA (eds) The liver: biology and pathobiology. Raven, New York, pp 819–838
Ghany MG, Hoofnagle JH (2015) Harrison’s principles of internal medicine, 19th edn. McGraw-Hill Education, New York, pp 1989–1995
Ghyselinck NB, Båvik C, Sapin V, Mark M, Bonnier D, Hindelang C, Dierich A, Nilsson CB, Håkansson H, Sauvant P, Azaïs-Braesco V, Frasson M, Picaud S, Chambon P (1999) Cellular retinol-binding protein I is essential for vitamin A homeostasis. EMBO J 18:4903–4914
Giancotti FG (2000) Complexity and specificity of integrin signaling. Nat Cell Biol 2:E13–E14
Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285:1028–1032
Gjøen T, Bjerkelund T, Blomhoff HK, Norum KR, Berg T, Blomhoff R (1987) Liver takes up retinol-binding protein from plasma. J Biol Chem 262:10926–10930
Gnainsky Y, Spira G, Paizi M, Bruck R, Nagler A, Abu-Amara SN, Geiger B, Genina O, Monsonego-Ornan E, Pines M (2004) Halofuginone, an inhibitor of collagen synthesis by rat stellate cells, stimulates insulin-like growth factor binding protein-1 synthesis by hepatocytes. J Hepatol 40:269–277
Goodman DW (1984) Plasma retinol-binding protein. In: Sporn MB, Roberts AB, Goodman DS (eds) The retinoids, vol 2. Academic, New York, pp 41–88
Goodman DS, Blomstrand R, Werner B, Huang HS, Shiratori T (1966) The intestinal absorption and metabolism of vitamin A and β-carotene in man. J Clin Invest 45:1615
Grab B, Miles AJ, Furcht LT, Fields GB (1996) Promotion of fibroblast adhesion by triple-helical peptide models of type I collagen-derived sequences. J Biol Chem 271:12234–12240
Graham TE, Yang Q, Blüher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson P-A, Smith U, Kahn BB (2006) Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. New Engl J Med 354:2552–2563
Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P (1986) Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 320:134–139
Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C (1991) Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets. J Biol Chem 266:11341–11346
Greenberg AS, Egan JJ, Wek SA, Moos MC Jr, Londos C, Kimmel AR (1993) Isolation of cDNAs for perilipins A and B: sequence and expression of lipid droplet-associated proteins of adipocytes. Proc Natl Acad Sci USA 90:12035–12039
Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J (1986) Sequence and expression of human estrogen receptor complementary DNA. Science 231:1150–1154
Greenwel P, Rubin J, Schwartz M, Hertzberg EL, Rojkind M (1993) Liver fat-storing cell clones obtained from a CCl4-cirrhotic rat are heterogeneous with regard to proliferation, expression of extracellular matrix components, interleukin-6, and connexin 43. Lab Invest 69:210–216
Greenwel P, Geerts A, Ogata I, Solis-Herruzo JA, Rojkind M (1994) Liver fibrosis. In: Arias IA, Boyer JL, Fausto N, Jakoby WB, Schachter DA, Shafritz DA (eds) The liver: biology and pathobiology. Raven, New York, pp 1367–1380
Gressner AM, Bachem MG (1990) Cellular sources of noncollagenous matrix proteins: role of fat-storing cells in fibrogenesis. Semin Liver Dis 10:30–46
Gressner AM, Bachem MG (1995) Molecular mechanisms of liver fibrogenesis-A homage to the role of activated fat-storing cells. Digestion 56:335–346
Gressner AM, Krul N, Bachem MG (1994) Regulation of proteoglycan expression in fibrotic liver and cultured fat-storing cells. Pathol Res Pract 190:864–882
Grinnell F, Ho CH, Tamariz E, Lee DJ, Skuta G (2003) Dendritic fibroblasts in three-dimensional collagen matrices. Mol Biol Cell 14:384–395
Grizzi F, Francescini B, Gagliano N, Moscheni C, Annoni G, Vdrgani C, Hermonat PL, Chiriva-Internati M, Dioguardi N (2003) Mast cell density, hepatic stellate cell activation and TGF-β1 transcripts in the aging Sprague-Dawley rat during early acute liver injury. Toxicol Pathol 31:173–178
Guimarães ELM, Franceschi MFS, Andrade CBM, Guaragna RM, Borojevic R, Margis R, Bernard EA, Guma FCR (2007) Hepatic stellate cell line modulates lipogenic transcription factors. Liver Int 27:1255–1264
Guo YT, Leng XS, Li T, Peng JR, Song SH, Xiong LF, Qin ZZ (2005) Effect of ligand of peroxisome proliferator-activated receptor γ on the biological characters of hepatic stellate cells. World J Gastroenterol 11:4735–4739
Guyot C, Lepreux S, Combe C, Doudnikoff E, Bioulac-Sage P, Balabaud C, Desmoulière A (2006) Hepatic fibrosis and cirrhosis: the (myo)fibroblastic cell subpopulations involved. Int J Biochem Cell Biol 38:135–151
Haber PS, Keogh GW, Apte MV, Moran CS, Stewart NL, Crawford DHG, Pirola RC, McCaughan GW, Ramm GA, Wilson JS (1999) Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis. Am J Pathol 155:1087–1109
Hammel P, Couvelard A, O’Toole D, Ratouis A, Sauvanet A, Flejou JF, Degott C, Belghiti J, Bernades P, Valla D, Ruszniewski P, Levy P (2001) Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. New Engl J Med 344:418–423
Hamy F, Verwaerde P, Helbecque N, Formstecher P, Henichart JP (1991) Nuclear targeting of a viral-cointernalized protein by a short signal sequence from human retinoic acid receptors. Bioconjug Chem 2:375–378
Harada K, Sato Y, Isse K, Ikeda H, Nakanuma Y (2008) Induction of innate immune response and absence of subsequent tolerance to dsRNA in biliary epithelial cells relate to the pathogenesis of biliary atresia. Liver Int 28:614–621
Hartland SN, Murphy F, Aucott RL, Abergel A, Zhou X, Waung J, Patel N, Bradshaw C, Collins J, Mann D, Benyon RC, Iredale JP (2009) Active matrix metalloproteinase-2 promotes apoptosis of hepatic stellate cells via the cleavage of cellular N-cadherin. Liver Int 29:966–978
Hata R (1996) Where am I? How a cell recognizes its positional information during morphogenesis. Cell Biol Int 20:59–65
Hata R, Nagai Y (1980) Differentiation of hepatocytes into type I collagen producing cells during primary culture in the presence of aphidicolin (inhibitor of DNA polymerase alpha). Biochem Int 1:567–573
Hata R, Ninomiya Y (1984) Hepatocytes (hepatic parenchymal cells) produce a major part of liver collagen in vivo. Biochem Int 8:181–186
Hata R, Senoo H (1989) L-Ascorbic acid 2-phosphate stimulates collagen accumulation, cell proliferation, and formation of a three-dimensional tissuelike substance by skin fibroblast. J Cell Physiol 138:8–16
Hata R, Senoo H (1992) Extracellular matrix system regulates cell growth, tissue formation, and cellular functions. Tiss Cult Res Commun 11:337–343
Hata R, Ninomiya Y, Nagai Y, Sakakibara K, Tsukada Y (1978) Active synthesis of collagen by albumin-producing liver parenchymal cell clones in culture. Proc Jpn Acad Ser B 54(7):391–396
Hata R, Ninomiya Y, Nagai Y, Tsukada Y (1980) Biosynthesis of interstitial type of collagen by albumin-producing rat liver parenchymal cell (hepatocyte) clones in culture. Biochemistry 19:169–176
Haughton EL, Tucker SJ, Marek CJ, Durward E, Leel V, Bascal Z, Monaghan T, Koruth M, Collie-Duguid E, Mann DA, Trim JE, Wright MC (2006) Pregnane X receptor activators inhibit human hepatic stellate cell transdifferentiation in vitro. Gastroenterology 131:194–209
Hazra S, Xiong S, Wang J, Rippe RA, Krishna V, Chatterjee K, Tsukamoto H (2004) Peroxisome proliferator-activated receptor γ induces a phenotypic switch from activated to quiescent hepatic stellate cells. J Biol Chem 279:11392–11401
Hebiguchi T, Mezaki Y, Morii M, Watanabe R, Yoshikawa K, Miura M, Imai K, Senoo H, Yoshino H (2015) Massive bowel resection upregulates the intestinal mRNA expression levels of cellular retinol binding protein II and apolipoprotein A-IV and alters the intestinal vitamin A status in rats. Int J Mol Med 35:724–730
Heid HW, Moll R, Schwetlick I, Rackwitz HR, Keenan TW (1998) Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res 294:309–321
Hellemans K, Grinko I, Rombouts K, Schuppan D, Geerts A (1999) All-trans and 9-cis retinoic acid alter rat hepatic stellate cell phenotype differentially. Gut 45:134–142
Hellemans K, Michalik L, Dittie A, Knorr A, Rombouts K, De Jong J, Heirman C, Quartier E, Schuit F, Wahli W, Geerts A (2003a) Peroxisome proliferator-activated receptor-β signaling contributes to enhanced proliferation of hepatic stellate cells. Gastroenterology 124:184–201
Hellemans K, Rombouts K, Quartier E, Dittie AS, Knorr A, Michalik L, Rogiers V, Schuit F, Wahli W, Geerts A (2003b) PPARβ regulates vitamin A metabolism-related gene expression in hepatic stellate cells undergoing activation. J Lipid Res 44:280–295
Hellemans K, Verbuyst P, Quartier E, Schuit F, Rombouts K, Chandraratna RA, Schuppan D, Geerts A (2004) Differential modulation of rat hepatic stellate phenotype by natural and synthetic retinoids. Hepatology 39:97–108
Hellerbrand C, Wang SC, Tsukamoto H, Brenner DA, Rippe R (1996) Expression of intercellular adhesion molecule 1 by activated hepatic stellate cells. Hepatology 24:670–676
Hellerbrand C, Jobin C, Licato LL, Sartor RB, Brenner DA (1998) Cytokines induce NF-κB in activated but not in quiescent rat hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 275:G269–G278
Hendriks HFJ, Verhoofstad WAMM, Brouwer A, de Leeuw AM, Knook DL (1985) Perisinusoidal fat-storing cells are the main vitamin A storing sites in rat liver. Exp Cell Res 160:138–149
Hendriks HFJ, Brouwer A, Knook DL (1987) The role of hepatic fat-storing (stellate) cells in retinoid metabolism. Hepatology 7:1368–1371
Hendriks HFJ, Blaner WS, Wennekers HM, Piantedosi R, Brouwer A, de Leeuw AM, Goodman DS, Knook DL (1988) Distribution of retinoids, retinoid-binding proteins and related parameters in different types of liver cells isolated from young and old rats. Eur J Biochem 171:237–244
Hendriks HFJ, Brouwer A, Knook DL (1990) Isolation, purification, and characterization of liver cell types. Methods Enzymol 190:49–58
Hepatic stellate cell nomenclature (letter) (1996) Hepatology 23:193
Higashi N, Senoo H (2003) Distribution of vitamin A-storing lipid droplets in hepatic stellate cells in liver lobules—a comparative study. Anat Rec Part A 271:240–248
Higashi N, Kojima N, Miura M, Imai K, Sato M, Senoo H (2004) Cell–cell junctions between mammalian (human and rat) hepatic stellate cells. Cell Tissue Res 317:35–43
Higashi N, Sato M, Kojima N, Irie T, Kawamura K, Mabuchi A, Senoo H (2005a) Vitamin A storage in hepatic stellate cells in the regenerating rat liver with special reference to zonal heterogeneity. Anat Rec 286A:899–907
Higashi N, Wake K, Sato M, Kojima N, Imai K, Senoo H (2005b) Degradation of extracellular matrix by extrahepatic stellate cells in the intestine of the lamprey, Lampetra japonica. Anat Rec 285A:668–675
Higashiyama R, Inagaki Y, Hong YY, Kushida M, Nakao S, Niioka M, Watanabe T, Okano H, Matsuzaki Y, Shiota G, Okazaki I (2007) Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Hepatology 45:213–222
Hirosawa K (1977) A note on autoradiography; an introduction of vitamin A-storing cells. Acta Histochem Cytochem 10:253–259
Hirosawa K, Yamada E (1973) The localization of the vitamin A in the mouse liver as revealed by electron microscope radioautography. J Electron Microsc 22:337–346
Hirosawa K, Kokubo Y, Kitamura M, Shiraishi T (1988) Fine structure of intestinal fibroblasts: autoradiographic and three-dimensional studies. J Electron Microsc 37:219–228
Holden C (1998) Polar bears and PCBs. Science 280:2053
Hollander D, Muralidhara KS (1977) Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport. Am J Physiol 232:F471–F477
Hollenberg SM, Weinberger C, Ong ES, Cerelli G, Oro A, Lebo R, Thompson EB, Rosenfeld MG, Evans RM (1985) Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318:635–641
Hong F, Tuyama A, Lee TF, Loke J, Agarwal R, Cheng X, Garg A, Fiel MI, Schwartz M, Walewski J, Branch A, Schecter AD, Bansal MB (2009) Hepatic stellate cells express functional CXCR4: role in stromal cell-derived factor-1a-mediated stellate cell activation. Hepatology 49:2055–2067
Horiuchi T (1960) Electron microscopic observation on the sinusoid of the normal rabbit liver. Kobe J Med Sci 6:185–210
Hruban Z, Russell, RM, Boyer JL, Glagov S, Bagheri SA (1974) Ultrastructural changes in livers of two patients with hypervitaminosis A. Am J Pathol 76:451–468
Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25
Igarashi M, Yogiashi Y, Mihara M, Takada I, Kitagawa H, Kato S (2007) Vitamin K induces osteoblast differentiation through pregnane X receptor-mediated transcriptional control of the Msx2 gene. Mol Cell Biol 27:7947–7954
Ikeda H, Fujiwara K (1995) Cyclosporin A and FK-506 in inhibition of rat Ito cell activation in vitro. Hepatology 21:1161–1166
Ikejima K, Takei Y, Honda H, Hirose M, Yoshikawa M, Zhang Y-J, Lang T, Fukuda T, Yamashina S, Kitamura T, Sato N (2002) Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 122:1399–1410
Imai K, Senoo H (1998) Morphology of sites of adhesion between hepatic stellate cells (vitamin A-storing cells) and a three-dimensional extracellular matrix. Anat Rec 250:430–437
Imai K, Senoo H (2000) Morphology of sites of adhesion between extracellular matrix and hepatic stellate cells. Connect Tissue 32:395–400
Imai K, Sato M, Kojima N, Miura M, Matano Y, Senoo H (1997) Three-dimensional morphological changes in cultured hepatic stellate cells by type I collagen fibers. In: Wisse E, Knook DL, Balabaud C (eds) Cells of the hepatic sinusoid, vol 6. Kupffer Cell Foundation, Leiden, pp 105–106
Imai K, Sato M, Kojima N, Miura M, Sato T, Sugiyama T, Enomoto K, Senoo H (2000a) Storage of lipid droplets in and production of extracellular matrix by hepatic stellate cells (vitamin A-storing cells) in Long-Evans cinnamon-like colored (LEC) rats. Anat Rec 258:338–348
Imai K, Sato T, Senoo H (2000b) Adhesion between cells and extracellular matrix with special reference to hepatic stellate cell adhesion to three-dimensional collagen fibers. Cell Struct Funct 25:329–336
Imanishi Y, Batten ML, Piston DW, Baehr W, Palczewski K (2004) Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye. J Cell Biol 164:373–383
Inagaki Y, Okazaki I (2007) Emerging insights into transforming growth factor β Smad signal in hepatic fibrogenesis. Gut 56:284–292
Inagaki Y, Higashi K, Kushida M, Hong YY, Nakao S, Higashiyama R, Moro T, Itoh J, Mikami T, Kimura T, Shiota G, Kuwabara I, Okazaki I (2008) Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-7. Gastroenterology 134:1180–1190
Ip E, Farrell G, Hall P, Robertson G, Leclercq I (2004) Administration of the potent PPARα agonist, Wy-14,643, reverses nutritional fibrosis and steatohepatitis in mice. Hepatology 39:1286–1296
Iredale JP (1997) Tissue inhibitors of metalloproteinases in liver fibrosis. Int J Biochem Cell Biol 29:43–54
Iredale JP (2003a) Regulating hepatic inflammation: pathogen-associated molecular patterns take their toll. Hepatology 37:979–982
Iredale JP (2003b) Cirrhosis: new research provides a basis for rational and targeted treatments. Br Med J 327:143–147
Iredale JP (2007) Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 117:539–548
Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ (1998) Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 102:538–549
Irie T, Kajiwara S, Kojima N, Senoo H, Seki T (2004) Retinal is the essential form of retinoid for storage and transport in the adults of the ascidian Halocynthia roretzi. Comp Biochem Physiol Part B 139:597–606
Issa R, Williams E, Trim N, Kendall T, Arthur MJP, Reichen J, Benyon RC, Iredale JP (2001) Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut 48:548–557
Itagaki T, Shimizu I, Cheng X, Yuan Y, Oshio A, Tamaki K, Fukuno H, Honda H, Okamura Y, Ito S (2005) Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells. Gut 54:1782–1789
Ito T (1951) Cytological studies on stellate cells of Kupffer and fat-storing cells in the capillary wall of the human liver. Acta Anat Nippon 26:42
Ito Y, Sørensen KK, Bethea NW, Svistounov D, McCuskey MK, Smedsrød B, McCuskey RS (2007) Age-related changes in the hepatic microcirculation of mice. Exp Gerontol 42:789–797
Izumi N, Mizuguchi S, Inagaki Y, Saika S, Kawada N, Nakajima Y, Inoue K, Suehiro S, Friedman SL, Ikeda K (2006) BMP-7 opposes TGF-β1-mediated collagen induction in mouse pulmonary myofibroblasts through Id2. Am J Physiol Lung Cell Mol Physiol 290:L120–L126
Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33:245–254
Janoschek N, van de Leur E, Gressner AM, Weiskirchen R (2004) Induction of cell death in activated hepatic stellate cells by targeted gene expression of the thymidine kinase/ganciclovir system. Biochem Biophys Res Commun 316:1107–1115
Jarman WM, Simon M, Norstrom RJ, Burns SA, Bacon CA, Simoneit BRT, Risebrough RW (1992) Global distribution of Tris(4-chlorophenyl)methanol in high trophic level birds and mammals. Environ Sci Technol 26:1770–1774
Jeong W, Osei-Hyiaman D, Park O, Liu J, Bátkai S, Mukhopadhyay P, Horiguchi N, Harvey-White J, Marsicano G, Lutz B, Gao B, Kunos G (2008) Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver. Cell Metab 7:227–235
Jiang HP, Serrero G (1992) Isolation and characterization of a full-length cDNA coding for an adipose differentiation-related protein. Proc Natl Acad Sci USA 89:7856–7860
Jiang F, Parsons CJ, Tefanovic B (2006) Gene expression profile of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway inactivation. J Hepatol 45:401–409
Jones PL, Schmidhauser C, Bissell MJ (1993) Regulation of gene expression and cell function by extracellular matrix. Crit Rev Eukaryot Gene Express 3:137–154
Kalinchenko VV, Bhattacharyya D, Zhou Y, Gussarova GA, Kim W, Shin B, Costa RH (2003) Foxf1+/− mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury. Hepatology 37:107–117
Kalluri R, Neilson EG (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 112:1776–1784
Kanai M, Raz A, Goodman DW (1968) Retinol-binding protein: the transport protein for vitamin A in human plasma. J Clin Invest 47:2025–2044
Kanaka-Gantenbein C, Margeli A, Pervanidou P, Sakka S, Mastorakos G, Chrousos GP, Papassotiriou I (2008) Retinol-binding protein 4 and lipocalin-2 in childhood and adolescent obesity: when children are not just “small adults”. Clin Chem 54:1176–1182
Kapanci Y, Ribaux C, Chaponnier C, Gabbiani G (1992) Cytoskeletal features of alveolar myofibroblasts and pericytes in normal human and rat lung. J Histochem Cytochem 40:1955–1963
Kato M, Kato K, Goodman DS (1984) Immunocytochemical studies on the localization of plasma and of cellular retinol-binding proteins and of transthyretin (prealbumin) in rat liver and kidney. J Cell Biol 98:1696–1704
Kawada N, Klein H, Decker K (1992) Eicosanoid-mediated contractility of hepatic stellate cells. Biochem J 285:367–371
Kawada N, Klein H, Decker K (1993a) Contraction and relaxation of hepatic stellate cells in culture. In: Knook DL, Wisse E (eds) Cells of the hepatic sinusoid, vol 4. Kupffer Cell Foundation, Leiden, pp 161–164
Kawada N, Tran-Thi T-A, Klein H, Decker K (1993b) The contraction of hepatic stellate (Ito) cells stimulated with vasoactive substances. Possible involvement of endothelin 1 and nitric oxide in the regulation of the sinusoidal tonus. Eur J Biochem 213:815–823
Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K (2001) Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells. J Biol Chem 276:25318–25323
Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H (2007) A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 315:820–825
Kida Y, Asahina K, Inoue K, Kawada N, Yoshizato K, Wake K, Sato T (2007) Characterization of vitamin A-storing cells in mouse fibrous kidneys using cygb/STAP as a marker of activated stellate cells. Arch Histol Cytol 70:95–106
Kidd M, Modlin IM, Shapiro MD, Camp RL, Mane SM, Usinger W, Murren JR (2007) CTGF, intestinal stellate cells and carcinoid fibrogenesis. World J Gastroenterol 13:5208–5216
Kisseleva T, Brenner DA (2006) Hepatic stellate cells and the reversal of fibrosis. J Gastroenterol Hepatol 21:S84–S87
Kisseleva T, Brenner DA (2007) Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis. J Gastroenterol Hepatol 22:S73–S78
Kisseleva T, Uchinami H, Feirt N, Quintana-Bustamante O, Segovia JC, Schwabe RF, Brenner DA (2006) Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J Hepatol 45:429–438
Klein I, Crispe IN (2006) Complete differentiation of CD8+ T cells activated locally within the transplanted liver. J Exp Med 203:437–447
Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW, Martin GR (1986) Basement membrane complexes with biological activity. Biochemistry 25:312–318
Knight V, Tchongue J, Lourensz D, Tipping P, Sievert W (2012) Protease-activated receptor 2 promotes experimental liver fibrosis in mice and activates human hepatic stellate cells. Hepatology 55:879–887
Knittel T, Aurisch S, Neubauer K, Eichhorst S, Ramadori G (1996) Cell-type-specific expression of neural cell adhesion molecule (N-CAM) in Ito cells of rat liver. Upregulation during in vitro activation and in hepatic tissue repair. Am J Pathol 149:449–462
Knittel T, Kobold D, Saile B, Grundmann A, Neubauer K, Piscaglia F, Ramadori G (1999) Rat liver myofibroblasts and hepatic stellate cells: different cell populations of the fibroblast lineage with fibrogenic potential. Gastroenterology 117:1205–1221
Knook DL, Blansjaar N, Sleyster EC (1977) Isolation and characterization of Kupffer and endothelial cells from the rat liver. Exp Cell Res 109:317–329
Knook DL, Seffelaar AM, de Leeuw AM (1982) Fat-storing cells of the rat liver. Their isolation and purification. Preliminary notes. Exp Cell Res 139:468–471
Kobayashi K, Takahashi Y (1971) Effect of the administration of large dose of vitamin A on the fine structure of rat liver with special reference to changes in the fat-storing cell. Arch Histol Jpn 33:421–443
Kobayashi K, Takahashi Y, Shibasaki S (1973) Cytological studies of fat-storing cells in the liver of rats given large doses of vitamin A. Nat New Biol 243:186–188
Koda H, Okuno M, Imai S, Moriwaki H, Muto Y, Kawada N, Kojima S (1996) Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-β. Biochem Biophys Res Commun 221:565–569
Kojima N, Miura M, Matano Y, Imai K, Sato M, Senoo H, Hata R (1997) Reversible regulation of hepatic stellate cell functions by three-dimensional structure of extracellular matrix. In: Wisse E, Knook DL, Balabaud C (eds) Cells of the hepatic sinusoid, vol 6. Kupffer Cell Foundation, Leiden, pp 107–109
Kojima N, Sato M, Imai K, Miura M, Senoo H (1998) Hepatic stellate cells (vitamin A-storing cells) change their cytoskeleton structure by extracellular matrix through signal transduction system. Histochem Cell Biol 110:121–128
Kojima N, Sato M, Miura M, Imai K, Senoo H (1999) Alteration in distribution of focal adhesion components by signaling inhibitors in hepatic stellate cells and fibroblasts cultured on type I collagen gel. In: Wisse E, Knook DL, de Zanger R, Fraser R (eds) Cells of the hepatic sinusoid, vol 7. Kupffer Cell Foundation, Leiden, pp 24–25
Kojima N, Sato M, Suzuki A, Sato T, Satoh S, Kato T, Senoo H (2001) Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liver. Hepatology 34:751–757
Kon K, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Kitamura T, Takei Y, Sato N (2002) Pioglitazone prevents early-phase hepatic fibrogenesis caused by carbon tetrachloride. Biochem Biophys Res Commun 291:55–61
Kornberg LJ, Earp HS, Tuener CE, Prockop C, Juliano RL (1991) Signal transduction by integrins: increased protein tyrosine-phosphorylation caused by clustering of β1 integrins. Proc Natl Acad Sci USA 88:8392–8396
Kozak M (1991) An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol 115:887–903
Kristensen DB, Kawada N, Imamura K, Miyamoto Y, Tateno C, Seki S, Kuroki T, Yoshizato K (2000) Proteome analysis of rat hepatic stellate cells. Hepatology 32:268–277
Krust A, Green S, Argos P, Kumar V, Walter P, Bornert JM, Chambon P (1986) The chicken oestrogen receptor sequence: homology with v-erbA and the human oestrogen and glucocorticoid receptors. EMBO J 5:891–897
Kubota H, Yao H-L, Reid LM (2007) Identification and characterization of vitamin A-storing cells in fetal liver: implications for functional importance of hepatic stellate cells in liver development and hematopoiesis. Stem Cells 25:2339–2349
Kupffer CV (1876) Ueber Sternzellen der Leber. Briefliche Mitteilung an Prof. Waldeyer. Arch Mikr Anat 12:353–358
Kupffer CV (1898) Ueber Sternzellen der Leber. Verh anat Ges 12: Versammulung in Kiel, pp 80–86
Kupffer CV (1899) Ueber die sogenannten Sternzellen der Sugethierleber. Arch Mikr Anat 54:254–288
Kurata S, Senoo H, Hata R-I (1993) Transcriptional activation of type I collagen genes by ascorbic acid 2-phosphate in human skin fibroblasts and its failure in cells from a patient with α2(I)-chain-defective Ehlers–Danlos syndrome. Exp Cell Res 206:63–71
Kusumoto Y, Fujita T (1977) Vitamin A uptake cells distributed in the liver and other organs of the rat. Arch Histol Jpn 40:121–136
Lang A, Schrum LW, Schoonhoven R, Tuvia S, Solís-Herruzo JA, Tsukamoto H, Brenner DA, Rippe RA (2000) Expression of small heat shock protein B-crystallin is induced after hepatic stellate cell activation. Am J Physiol Gastrointest Liver Physiol 279:G1333–G1342
Lawrence CW, Crain FD, Lotspeich FJ, Krause RF (1966) Absorption, transport, and storage of retinyl-15-14C palmitate-9,10-3H in the rat. J Lipid Res 7:226–229
Le Couteur DG, Warren A, Cogger VC, Smedsrød B, Sørensen KK, De Cabo R, Fraser R, McCuskey RS (2008) Old age and the hepatic sinusoid. Anat Rec 291:672–683
Leclercq IA, Sempoux C, Starkel P, Horsmans Y (2006) Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats. Gut 55:1020–1029
Leo MA, Lieber CS (1983) Hepatic fibrosis after long-term administration of ethanol and moderate vitamin A supplementation in the rat. Hepatology 3:1–11
Lepreux S, Bioulac-Sage P, Gabbiani G, Sapin V, Housset C, Rosenbaum J, Balabaud C, Desmoulière A (2004) Cellular retinol-binding protein-1 expression in normal and fibrotic/cirrhotic human liver: different patterns of expression in hepatic stellate cells and (myo)fibroblast subpopulations. J Hepatol 40:774–780
Levine D, Rockey DC, Milner TA, Breuss JM, Fallon JT, Schnapp LM (2000) Expression of the integrin α8β1. Am J Pathol 156:1927–1935
Levin MS (1993) Cellular retinol-binding proteins are determinants of retinol uptake and metabolism in stably transfected Caco-2 cells. J Biol Chem 268: 8267–8276
Li D, Friedman SL (2001) Hepatic stellate cells: Morphology, function, and regulation. In: Arias IM, Boyer JL, Chisari FV, Fausto N, Schachter D, Shafritz DA (eds) The liver: biology and pathobiology, 4th edn. Lippincott Williams and Wilkins, Philadelphia, pp 455–468
Li YL, Sato M, Kojima N, Miura M, Senoo H (1999) Regulatory role of extracellular matrix components in expression of matrix metalloproteases in cultured hepatic stellate cells. Cell Struct Funct 24:255–261
Lin J, Chen A (2008) Activation of peroxisome proliferator-activated receptor-γ by curcumin blocks the signaling pathways for PDGF and EGF in hepatic stellate cells. Lab Invest 88:529–540
Lindsay CK, Thorgeirsson UP (1995) Localization of messenger RNA for tissue inhibitor of metalloproteinases-1 and type IV collagenases/gelatinases in monkey hepatocellular carcinomas. Clin Exp Metastasis 13:381–388
Loreal O, Levavasseur F, Fromaget C, Gros D, Guillouzo A, Clement B (1993) Cooperation of Ito cells and hepatocytes in deposition of an extracellular matrix in vitro. Am J Pathol 143:538–544
Lu X, Gruia-Gray J, Copeland NG, Gilbert DJ, Jenkins NA, Londos C, Kimmel AR (2001) The murine perilipin gene: the lipid droplet-associated perilipins derive from tissue-specific, mRNA splice variants and define a gene family of ancient origin. Mamm Genome 12:741–749
Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS, Wilson EM (1988) Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 240:327–330
Ma X, Svegliati-Baroni G, Poniachik J, Baraona E, Lieber CS (1997) Collagen synthesis by liver stellate cells is released from its normal feedback regulation by acetaldehyde-induced modification of the carboxyl-terminal propeptide of procollagen. Alcohol Clin Exp Res 21:1204–1211
Mabuchi A, Mullaney I, Sheard PA, Hessian PA, Mallard BL, Tawadrous MN, Zimmermann A, Senoo H, Wheatley AM (2004) Role of hepatic stellate cells in the early phase of liver regeneration in rat: formation of tight adhesions to parenchymal cells. J Hepatol 40:910–916
MacDonald PN, Ong DE (1988) A lecithin:retinol acyltransferase activity in human and rat liver. Biochem Biophys Res Commun 156:157–163
Mackay IR (2002) Hepatoimmunology: a perspective. Immunol Cell Biol 80:36–44
Maeda N, Kawada N, Seki S, Arakawa T, Ikeda K, Iwao H, Okuyama H, Hirabayashi J, Kasai K, Yoshizato K (2003) Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways. J Biol Chem 278:18938–18944
Magness ST, Bataller R, Yang L, Brenner DA (2004) A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations. Hepatology 40:1151–1159
Majno G (1979) The story of the myofibroblasts. Am J Surg Pathol 6:535–542
Maksvytis HJ, Vaccaro C, Brody JS (1981) Isolation and characterization of the lipid-containing interstitial cell from the developing rat lung. Lab Invest 45:248–259
Maksvytis HJ, Niles RM, Simanovsky L, Minassian IA, Richardson LL, Hamosh M, Hamosh P, Brody JS (1984) In vitro characteristics of the lipid-filled interstitial cell associated with postnatal lung growth: evidence for fibroblast heterogeneity. J Cell Physiol 118:113–123
Malaba L, Smeland S, Senoo H, Norum KR, Berg T, Blomhoff R, Kindberg GM (1995) Retinol-binding protein and asialo-orosomucoid are taken up by different pathways in liver cells. J Biol Chem 270:15686–15692
Malhi H, Gores GJ (2008) Cellular and molecular mechanisms of liver injury. Gastroenterology 134:1641–1654
Mallat A, Preaux A-M, Blazejewski S, Rosenbaum J, Dhumeaux D, Mavier P (1995) Interferon alfa and gamma inhibit proliferation and collagen synthesis of human Ito cells in culture. Hepatology 21:1003–1010
Mallat A, Gallois C, Tao J, Habib A, Maclouf J, Mavier P, Préaux A-M, Lotersztajn S (1998) Platelet-derived growth factor-BB and thrombin generate positive and negative signals for human hepatic stellate cell proliferation. J Biol Chem 273:27300–27305
Mann DA, Smart DE (2002) Transcriptional regulation of hepatic stellate cell activation. Gut 50:891–896
Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA (2007) Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ 14:275–285
Marek CJ, Tucker SJ, Konstantinou DK, Elrick LJ, Haefner D, Sigalas C, Murray GI, Goodwin B, Wright MC (2005) Pregnenolone-16α-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms. Biochem J 387:601–608
Margis R, Borojevic R (1989) Retinoid-mediated induction of the fat-storing phenotype in a liver connective tissue cell line (GRX). Biochim Biophys Acta Mol Cell Res 1011:1–5
Margueron R, Trojer P, Reinberg D (2005) The key to development: interpreting the histone code? Curr Opin Genet Dev 15:163–176
Marra F (2006) Thiazolidinediones and hepatic fibrosis: don’t wait too long. Gut 55:917–919
Marra F, Pinzani M, DeFranco R, Laffi G, Gentilini P (1995) Involvement of phosphatidylinositol 3-kinase in the activation of extracellular signal-regulated kinase by PDGF in hepatic stellate cells. FEBS Lett 376:141–145
Marra F, Efsen E, Romanelli RG, Caligiuri A, Pastacaldi S, Batignani G, Bonacchi A, Caporale R, Laffi G, Pinzani M, Gentilini P (2000) Ligands of peroxisome proliferator-activated receptor γ modulate profibrogenic and proinflammatory actions in hepatic stellate cells. Gastroenterology 119:466–478
Marshall AHE (1956) An Outline of the Cytology and Pathology of the Reticular Tissue. Thomas, Springfield, Illinois
Martin G, Sewell B, Yeomans ND, Smallwood RA (1992) Ageing has no effect on the volume density of hepatocytes, reticulo-endothelial cells or the extracellular space in livers of female Sprague-Dawley rats. Clin Exp Pharmacol Physiol 19:537–539
Martinez-Hernandez A (1984) The hepatic extracellular matrix. I. Electron immunohistochemical studies in normal rat liver. Lab Invest 51:57–73
Martinez-Hernandez A, Amenta PS (1993a) The hepatic extracellular matrix. I. Components and distribution in normal liver. Virchows Arch A Pathol Anat 423:1–11
Martinez-Hernandez A, Amenta PS (1993b) The hepatic extracellular matrix. II. Ontogenesis, regeneration and cirrhosis. Virchows Arch A Pathol Anat 423:77–84
Martinez-Hernandez A, Amenta PS (1995) The extracellular matrix in hepatic regeneration. FASEB J 9:1401–1410
Martucci EB, Ziulkoski AL, Fortuna VA, Guaragna AM, Guma FCR, Trugo LC, Borojevic R (2004) β-Carotene storage, conversion to retinoic acid, and induction of the lipocyte phenotype in hepatic stellate cells. J Cell Biochem 92:414–423
Masamune A, Kikuta K, Satoh M, Sakai Y, Satoh A, Shimosegawa T (2002) Ligands of peroxisome proliferator-activated receptor-γ block activation of pancreatic stellate cells. J Biol Chem 277:141–147
Masamune A, Kikuta K, Watanabe T, Satoh K, Hirota M, Shimosegawa T (2008) Hypoxia stimulates pancreatic stellate cells to induce fibrosis and angiogenesis in pancreatic cancer. Am J Physiol Gastrointest Liver Physiol 295:G709–G717
Matano Y, Miura M, Kojima N, Sato M, Imai K, Senoo H (1999) Hepatic stellate cells and extrahepatic stellate cells (extrahepatic vitamin A-storing cells). In: Wisse E, Knook DL, de Zanger R, Fraser R (eds) Cells of the hepatic sinusoid, vol 7. Kupffer Cell Foundation, Leiden, pp 26–27
Matsumoto E, Hirosawa K (1983) Some observations on the structure of Suncus liver with special reference to the vitamin A-storing cells. Am J Anat 167:193–204
Matsumoto Y, Itami S, Kuroda M, Yoshizato K, Kawada N, Murakami Y (2016) MiR-29a assists in preventing the activation of human stellate cells and promotes recovery from liver fibrosis in mice. Mol Ther. doi:10.1038/mt.127
Matsuura T, Nagamori S, Fujise K, Hasumura S, Homma S, Sujino H, Shimizu K, Niiya M, Kameda H, Hirosawa K (1989) Retinol transport in cultured fat-storing cells of rat liver. Quantitative analysis by anchored cell analysis and sorting system. Lab Invest 61:107–115
Matsuura T, Nagamori S, Hasumura S, Sujino H, Shimizu K, Niiya M, Hirosawa K (1993) Retinol transport in cultured stellate cells of rat liver: studies by light and electron microscope autoradiography. Exp Cell Res 206:111–118
Matsuura T, Hasumura S, Nagamori S (1999) Retinol esterification activity contributes to retinol transport in stellate cells. Cell Struct Funct 24:111–116
McCarroll JA, Phillips PA, Kjumar RK, Park S, Pirola RC, Wilson JS, Apte MV (2004) Pancreatic stellate cell migration: role of the phosphatidylinositol 3-kinase (PI3-kinase) pathway. Biochem Pharmacol 67:1215–1225
McClain CJ, Van Thiel DH, Parker S, Badzin LK, Gilbert H (2008) Alterations in zinc, vitamin A, and retinol-binding protein in chronic alcoholics: a possible mechanism for night blindness and hypogonadism. Alcohol Clin Exp Res 3:135–141
McCuskey RS (2008) The hepatic microvascular system in health and its response to toxicants. Anat Rec 291:661–671
McDonnell DP, Mangelsdorf DJ, Pike JW, Haussler MR, O’Malley BW (1987) Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science 235:1214–1217
Melton AC, Datta A, Yee HF Jr (2006) [Ca2+]i-independent contractile force generation by rat hepatic stellate cells in response to endothelin-1. Am J Physiol Gastrointest Liver Physiol 290:G7–G13
Menke A, Yamaguchi H, Gress TN, Adler G (1997) Extracellular matrix is reduced by inhibition of transforming growth factor beta1 in pancreatitis in the rat. Gastroenterology 113:295–303
Mercier I, Lechaire JP, Desmoulière A, Gaill F, Aumailley M (1996) Interactions of human skin fibroblasts with monomeric or fibrillar collagens induce different organization of cytoskeleton. Exp Cell Res 225:245–256
Messing A (1999) Nestin in the liver-Lessons from the brain. Hepatology 29:602–603
Mezaki Y, Yoshikawa K, Yamaguchi N, Miura M, Imai K, Kato S, Senoo H (2007) Rat hepatic stellate cells acquire retinoid responsiveness after activation in vitro by post-transcriptional regulation of retinoic acid receptor alpha gene expression. Arch Biochem Biophys 465:370–379
Mezaki Y, Yamaguchi N, Yoshikawa K, Miura M, Imai K, Itoh H, Senoo H (2009) Insoluble speckled cytosolic distribution of retinoic acid receptor alpha protein as a marker of hepatic stellate cell activation in vitro. J Histochem Cytochem 57:687–699
Mezaki M, Morii M, Yoshikawa K, Yamaguchi N, Miura M, Imai K, Yoshino H, Senoo H (2012a) Characterization of a cellular retinol binding protein from lamprey, Lethenteron japonicum. CBP Part B: Biochem Mol Biol 161:233–239
Mezaki Y, Morii M, Yoshikawa K, Yamaguchi N, Satoyoshi K, Miura M, Imai K, Hebuguchi T, Habuchi T, Senoo H (2012b) Elevated expression of transforming growth factor β3 in carbon tetrachloride-treated rat liver and involvement of retinoid signaling. Int J Mol Med 29:18–24
Mezaki Y, Morii M, Hebiguchi T, Yoshikawa K, Yamaguchi N, Miura M, Imai K, Yoshino H, Senoo H (2013a) Differential increases in the expression of intermediate filament proteins and concomitant morphological changes of transdifferentiating rat hepatic stellate cells observed in vitro. Acta Histochem Cytochem 46:137–143
Mezaki Y, Morii M, Hebiguchi T, Yoshikawa K, Yamaguchi N, Yoshino H, Senoo H (2013b) The role of retinoic acid receptors in activated hepatic stellate cells. Med Hypothesis 81:222–224
Michalopoulos GK, Bowen WC, Zajac VF, Beer-Stolz D, Watkins S, Kostrubsky V, Strom SC (1999) Morphogenetic events in mixed cultures of rat hepatocytes and nonparenchymal cells maintained in biological matrices in the presence of hepatocyte growth factor and epidermal growth factor. Hepatology 29:90–100
Migita K, Maeda Y, Abiru S, Komori A, Yokoyama T, Takii Y, Nakamura M, Yatsuhashi H, Eguchi K, Ishibashi H (2005) Peroxynitrite-mediated matrix metalloproteinase-2 activation in human hepatic stellate cells. FEBS Lett 579:3119–3125
Mitaka T, Mikami M, Sattler GL, Pitot HC, Mochizuki Y (1992) Small cell colonies appear in the primary culture of adult rat hepatocytes in the presence of nicotinamide and epidermal growth factor. Hepatology 16:440–447
Mitaka T, Sato F, Mizuguchi T, Yokono T, Mochizuki Y (1999) Reconstruction of hepatic organoid by rat small hepatocytes and hepatic nonparenchymal cells. Hepatology 29:111–125
Miura M, Sato M, Toyoshima I, Senoo H (1997) Extension of long cellular processes of hepatic stellate cells cultured on extracellular type I collagen gel by microtubule assembly: observation utilizing time-lapse video-microscopy. Cell Struct Funct 22:487–492
Miura M, Sato M, Toyoshima I, Senoo H (1999) Elongation of long, multipolar processes in hepatic stellate cell culture on type I collagen gel by microtubule assembly: observation utilizing time-lapse video-microscopy. In: Wisse E, Knook DL, de Zanger R, Fraser R (eds) Cells of the hepatic sinusoid, vol 7. Kupffer Cell Foundation, Leiden, pp 17–20
Miura S, Gan JW, Brzostowski J, Parisi MJ, Schultz CJ, Londos C, Oliver B, Kimmel AR (2002) Functional conservation for lipid storage droplet association among perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium. J Biol Chem 277:32253–32257
Miura M, Mezaki Y, Morii M, Hebiguchi T, Yoshino H, Kawatsu K, Imai K, Senoo H (2012/2013) Histology of the hepatopancreas of puffer fish (Takifugu rubripes) in relation to the localization of tetrodotoxin. Arch Histol Cytol 74:59–70
Miyahara T, Schrum L, Rippe R, Xiong S, Yee HF Jr, Motomura K, Anania FA, Willson TM, Tsukamoto H (2000) Peroxisome proliferator-activated receptors and hepatic stellate cell activation. J Biol Chem 275:35715–35722
Miyata E, Masuya M, Yoshida S, Nakamura S, Kato K, Sugimoto Y, Shibasaki T, Yamamura K, Ohishi K, Nishii K, Ishikawa F, Shiku H, Katayama N (2008) Hematopoietic origin of hepatic stellate cells in the adult liver. Blood 111:2427–2435
Montfort I, Pérez-Tamayo R, Alvizouri AM, Tello E (1990) Collagenase of hepatocytes and sinusoidal liver cells in the reversibility of experimental cirrhosis of the liver. Virchows Arch B Cell Pathol 59:281–289
Moore KL, Persaud TVN, Torchia MG (2008) The developing human: clinically oriented embryology, 8th edn. Saunders, Philadelphia
Morii M, Mezaki Y, Yamaguchi N, Yoshikawa K, Miura M, Imai K, Yoshino H, Hebiguchi T, Hebiguchi T, Senoo H (2010) Onset of apoptosis in cystic duct during metamorphosis of a Japanese lamprey, Lethenteron reissneri. Anat Rec 293:1155–1166
Morii M, Mezaki Y, Yoshikawa K, Miura M, Imai K, Hebuguchi T, Watanabe R, Asanuma Y, Yoshino H, Senoo H (2011) Cholestasis. In: Tripodi V (ed) How do lampreys avoid cholestasis after bile duct degeneration. INTECH, Rijeka, pp 81–98. ISBN 979-953-307-187-8
Moriwaki H, Blaner WS, Piantedosi R, Goodman DS (1988) Effects of dietary retinoid and triglyceride on the lipid composition of rat liver stellate cells and stellate cell lipid droplets. J Lipid Res 29:1523–1534
Mousavi SA, Sato M, Sporstøl M, Smedsrød B, Berg T, Kojima N, Senoo H (2005) Uptake of collagen into hepatic stellate cells: evidence of the involvement of urokinase plasminogen activator associated protein/Endo 180. Biochem J 387:39–46
Muir DCG, Wagemann R, Harrave BT, Thomas DJ, Peakall DB, Norstrom RJ (1992) Arctic marine ecosystem contamination. Sci Total Environ 122:75–134
Murakami K, Abe T, Miyazawa M, Yamaguchi M, Masuda T, Matsuura T, Nagamori S, Takeuchi K, Abe K, Kyogoku M (1995) Establishment of a new human cell line, LI90, exhibiting characteristics of hepatic Ito (fat-storing) cells. Lab Invest 72:731–739
Murphy DJ, Vance J (1999) Mechanisms of lipid-body formation. Trends Biochem Sci 24:109–115
Musso O, Rehn M, Saarela J, Théret N, Liétard J, Hintikka E, Lotrian D, Campion J-P, Pihlajaniemi T, Clément B (1998) Collagen XVIII is localized in sinusoids and basement membrane zones and expressed by hepatocytes and activated stellate cells in fibrotic human liver. Hepatology 28:98–107
Muto M (1975) A scanning electron microscopic study on endothelial cells and Kupffer cells in rat liver sinusoids. Arch Histol Jpn 37:269–386
Muto Y, Shidoji Y, Kanda Y (1982) Isolation and characterization of serum retinol-binding protein. In: Parker L (ed) Methods in enzymology, vol 81. Elsevier, Amsterdam pp 840–852
Nagatsuma K, Hayashi Y, Hano H, Sagara H, Murakami K, Saito M, Masaki T, Lu T, Tanaka M, Enzan H, Aizawa Y, Tajiri H, Matsuura T (2009) Lecithin:retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver. Liver Int 29:47–54
Nagy NE, Holven KB, Roos N, Senoo H, Kojima N, Norum KR, Blomhoff R (1997) Storage of vitamin A in extrahepatic stellate cells in normal rats. J Lipid Res 38:645–658
Nakagawa M, Nakabayashi H, Nakano H (1991) A simple method for the isolation of human Ito cells (fat-storing cells). Acta Hepatol Jpn 45:169–174
Nakatani K, Okuyama H, Shimahara Y, Saeki S, Kim D-H, Nakajima Y, Seki S, Kawada N, Yoshizato K (2004) Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis. Lab Invest 84:91–101
Napoli JL (1993) Biosynthesis and metabolism of retinoic acid: roles of CRBP and CRABP in retinoic acid homeostasis. J Nutr 123:362–366
Napoli JL (1999) Interactions of retinoid binding proteins and enzymes in retinoid metabolism. Biochim Biophys Acta 1440:139–162
Neesse A, Wagner M, Ellenrieder V, Bachem M, Gress TM, Buchholz M (2007) Pancreatic stellate cells potentiate proinvasive effects of SERPINE2 expression in pancreatic cancer xenograft tumors. Pancreatology 7:380–385
Neubauer K, Knittel T, Aurisch S, Fellmer P, Ramadori G (1996) Glial fibrillary acidic protein—a cell type specific marker for Ito cells in vivo and in vitro. J Hepatol 24:719–730
Newcomer ME, Ong DE (1990) Purification and crystallization of a retinoic acid-binding protein from rat epididymis. J Biol Chem 265:12876–12879
Nieto N, Greenwel P, Friedman SL, Zhang F, Dannenberg AJ, Cederbaum AI (2000) Ethanol and arachidonic acid increase α2(I) collagen expression in rat hepatic stellate cells overexpressing cytochrome P450 2E1. Role of H2O2 and cyclooxygenase-2. J Biol Chem 275:20136–20145
Niki T, De Bleser PJ, Xu G, Van den Berg K, Wisse E, Geerts A (1996) Comparison of glial fibrillary acidic protein and desmin staining in normal and CCl4-induced fibrotic rat livers. Hepatology 23:1538–1545
Niki T, Penky M, Hellemans K, De Bleser P, Van den Berg K, Vaeyens F, Quartier E, Schuit F, Geerts A (1999) Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 29:520–527
Nilsson M, Berg T (1977) Uptake and degradation of formaldehyde-treated 125I-labelled human serum albumin in rat liver cells in vivo and in vitro. Biochim Biophys Acta 497:171–182
Nilsson A, Trøen G, Petersen LB, Reppe S, Norum KR, Blomhoff R (1997) Retinyl ester storage is altered in liver stellate cells and in HL60 cells transfected with cellular retinol-binding protein type I. Int J Biochem Cell Biol 29:381–389
Nilsson CB, Hoegberg P, Trossvik C, Azaïs-Bræsco V, Blaner WS, Fex G, Harrison EH, Nau H, Schmidt CK, van Bennekum AM, Håkansson H (2000) 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases serum and kidney retinoic acid levels and kidney retinol esterification in the rat. Toxicol Appl Pharmacol 169:121–131
Nishimura T, Nakano T (2000) Immunocytochemical localization of bovine serum albumin (BSA) in the liver and testis of rats injected with testosterone-BSA, hydrocortisone-BSA or corticosterone-BSA. Cell Struct Funct 25:161–169
Norum KR (1984) The name of the perisinusoidal stellate cells, fat storing cells, Ito cells, pericyte, vitamin A storing cells of the liver. Kupffer Cell Bull 5:13
Noy N (2000) Retinoid-binding proteins: mediators of retinoid action. Biochem J 348:481–495
O’Byrne SM, Wongsiriroj N, Libien J, Vogel S, Goldberg IJ, Baehr W, Palczewski K, Blaner WS (2005) Retinoid absorption and storage is impaired in mice lacking lecithin:retinol acyltransferase (LRAT). J Biol Chem 280:35647–35657
Oakley F, Trim N, Constandinou CM, Ye W, Gray AM, Frantz G, Hillan K, Kendall T, Benyon AC, Mann DA, Iredale JP (2003) Hepatocytes express nerve growth factor during liver injury. Evidence for paracrine regulation of hepatic stellate cell apoptosis. Am J Pathol 163:1849–1858
Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, May MJ, Millward-Sadler H, Wright MC, Mann DA (2005) Inhibition of inhibitor of kB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology 128:108–120
Oben JA, Yang S, Lin H, Ono M, Mae Diehl A (2003) Norepinephrine and neuropeptide Y promote proliferation and collagen gene expression of hepatic myofibroblastic stellate cells. Biochem Biophys Res Commun 302:685–690
Ohata M, Lin M, Satre M, Tsukamoto H (1997) Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis. Am J Physiol 272:G589–G596
Oide H, Thurman RG (1994) Hepatic Ito cells contain calcium channels: increases with transforming growth factor-β1. Hepatology 20:1009–1014
Oikawa H, Masuda T, Kawaguchi J, Sato R (2002) Three-dimensional examination of hepatic stellate cells in rat liver and response to endothelin-1 using confocal laser scanning microscopy. J Gastroenterol Hepatol 17:861–872
Okabe T, Yorifuji H, Yamada E, Takaku F (1984) Isolation and characterization of vitamin A-storing lung cells. Exp Cell Res 154:125–135
Okuno M, Muto Y, Moriwaki H, Kato M, Noma A, Yagaya O, Nozaki Y, Suzuki Y (1990) Inhibitory effect of acyclic (polyprenoic acid) on hepatic fibrosis in CCl4-treated rats. Gastroenterol Jpn 25:223–229
Okuno M, Moriwaki H, Imai S, Muto Y, Kawada N, Suzuki Y, Kojima S (1997) Retinoids exacerbate rat liver fibrosis by inducing the activation of latent TGF-β in liver stellate cells. Hepatology 26:913–921
Okuno M, Sato T, Kitamoto T, Imai S, Kawada N, Suzuki Y, Yoshimura H, Moriwaki H, Onuki K, Masushige S, Muto Y, Friedman SL, Kato S, Kojima S (1999) Increased 9,13-di-cis-retinoic acid in rat hepatic fibrosis: implication for a potential link between retinoid loss and TGF-β mediated fibrogenesis in vivo. J Hepatol 30:1073–1080
Okuno M, Kojima S, Akita K, Matsushima-Nishiwaki R, Adachi S, Sano T, Takano Y, Takai K, Obora A, Yasuda I, Shiratori Y, Okano Y, Shimada J, Suzuki Y, Muto Y, Moriwaki H (2002) Retinoids in liver fibrosis and cancer. Front Biosci 7:d204–d218
Olaso E, Ikeda K, Eng FJ, Xu L, Wang L-H, Lin HC, Friedman SL (2001) DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest 108:1369–1378
Ong DE (1994) Absorption of vitamin A. In: Blomhoff R (ed) Vitamin A in health and disease. Marcel Dekker, New York, pp 37–72
Ong DE, MacDonald PN, Gubitosi AM (1988) Esterification of retinol in rat liver. Possible participation by cellular retinol-binding protein and cellular retinol-binding protein II. J Biol Chem 263:5789–5796
Ong DE, Newcomer M, Lareyre J-J, Orgebin-Crist M-C (2000) Epididymal retinoic acid-binding protein. Biochim Biophys Acta Prot Struct Mol Enzymol 1482:209–217
Orland MD, Anwar K, Cromley D, Chu CH, Chen L, Billheimer JT, Hussain MM, Cheng D (2005) Acyl coenzyme A dependent retinol esterification by acyl coenzyme A:diacylglycerol acyltransferase 1. Biochim Biophys Acta 1737:76–82
Paik Y-H, Schwabe RF, Bataller R, Russo MP, Jobin C, Brenner DA (2003) Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology 37:1043–1055
Paik J, Vogel S, Quadro L, Piantedosi R, Gottesman M, Lai K, Hamberger L, de Morais Vieira M, Blaner WS (2004) Vitamin A: overlapping delivery pathways to tissues from the circulation. J Nutr 134:276S–280S
Paradis V, Dargere D, Bonvoust F, Vidaud M, Segarini P, Bedossa P (2002) Effects and regulation of connective tissue growth factor on hepatic stellate cells. Lab Invest 82:767–774
Parsons CJ, Bradford BU, Pan CQ, Cheung E, Schauer M, Knorr A, Krebs B, Kraft S, Zahn S, Brocks B, Feirt N, Mei B, Cho M-S, Ramamoorthi R, Roldan G, Ng P, Lum P, Hirth-Dietrich C, Tomkinson A, Brenner DA (2004) Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats. Hepatology 40:1106–1115
Parsons CJ, Takashima M, Rippe RA (2007) Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol 22:S79–S84
Pasutto F, Sticht H, Hammersen G, Gillessen-Kaesbach G, FitzPatrick DR, Nürnberg G, Brasch F, Schirmer-Zimmermann H, Tolmie JL, Chitayat D, Houge G, Fernández-Martínez L, Keating S, Mortier G, Hennekam RCM, von der Wense A, Slavotinek A, Meinecke P, Bitoun P, Becker C, Nürnberg P, Reis A, Rauch A (2007) Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. Am J Human Genet 80:550–560
Pérez-Pomares JM, Carmona R, González-Iriarte M, Macías D, Guadix JA, Muñoz-Chápuli R (2004) Contribution of mesothelium-derived cells to liver sinusoids in avian embryos. Dev Dyn 229:465–474
Petkovich M, Brand NJ, Krust A, Chambon P (1987) A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330:444–450
Petta S, Cammà C, Di Marco V, Alessi N, Barbaria F, Cabibi D, Caldarella R, Ciminnisi S, Licata A, Massenti MF, Mazzola A, Tarantino G, Marchesini G, Craxì A (2008) Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis C virus genotype. Hepatology 48:28–37
Pfuhl W (1932) Moellendorff's Handbuch der mikroskopishen Anatomie des Menscen. V/2 BD. Verdauungsapprat. Die Leber
Phillips PA, McCarroll JA, Park S, Wu M-J, Pirola R, Korsten M, Wilson JS, Apte MV (2003a) Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Gut 52:275–282
Phillips PA, Wu MJ, Kjumar RK, Doherty E, McCarroll JM, Park S, Pirola RC, Wilson JS, Apte MV (2003b) Cell migration: a novel aspect of pancreatic stellate cell biology. Gut 52:677–682
Picard D, Yamamoto KR (1987) Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J 6:3333–3340
Pinzani M (1999) New kids on the block: pancreatic stellate cells enter the fibrogenesis world. Gut 44:451–452
Pinzani M (2004) Therapies for hepatic fibrosis: real hope or just academic exercise? Dig Liver Dis 36:714–716
Pinzani M (2006) Pancreatic stellate cells: new kids become mature. Gut 55:12–14
Pinzani M, Marra F (2001) Cytokine receptors and signaling in hepatic stellate cells. Semin Liver Dis 21:397–416
Pinzani M, Gesualdo L, Sabbah GM, Abboud HE (1989) Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. J Clin Invest 84:1786–1793
Pinzani M, Gentilini P, Abboud HE (1992) Phenotypical modulation of liver fat-storing cells by retinoids. Influence on unstimulated and growth factor-induced cell proliferation. J Hepatol 14:211–220
Pinzani M, Marra F, Carloni V (1998) Signal transduction in hepatic stellate cells. Liver 18:2–13
Pinzani M, Rombouts K, Colagrande S (2005) Fibrosis in chronic liver diseases: diagnosis and management. J Hepatol 42:S22–S36
Polonsky KS (2006) Retinol-binding protein 4, insulin resistance, and type 2 diabetes. New Engl J Med 354:2596–2598
Ponfick E (1869) Studien ueber die Schiksale koerniger Farbstoffe im Organismus. Virchow Arch Path Anat 48:1–55
Popper H (1941) Histologic distribution of vitamin A in human organs under normal and under pathologic conditions. Arch Pathol 31:766–802
Popper H (1944) Distribution of vitamin A in tissue as visualized by fluorescence microscopy. Physiol Rev 24:205–224
Popper H, Volk BW (1944) Absorption of vitamin A in the rat. Arch Pathol 38:71–75
Popper H, Steigmann F, Meyer KA, Zevin SS (1943) Relation between hepatic and plasma concentrations of vitamin A in human beings. Arch Int Med 72:439–460
Porter SB, Fraker LD, Chytil F, Ong DE (1983) Localization of retinol-binding protein in several tissues. Proc Natl Acad Sci USA 80:6586–6590
Potter JJ, Womack L, Mezey E, Anania FA (1998) Transdifferentiation of rat hepatic stellate cells results in leptin expression. Biochem Biophys Res Commun 244:178–182
Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling M-H, Albrecht J, PEG-FIBROSIS Project Group (2002) Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122:1303–1313
Prickett TCR, McKenzie JL, Hart DNJ (1988) Characterization of interstitial dendritic cells in human liver. Transplantation 46:754–761
Purohit V, Brenner DA (2006) Mechanisms of alcohol-induced hepatic fibrosis: a summary of the Ron Thurman symposium. Hepatology 43:872–878
Purohit V, Gao B, Song B-J (2009) Molecular mechanisms of alcoholic fatty liver. Alcohol Clin Exp Res 33:191–205
Purton MD (1976) Extravasucular cells within perisinusoidal space of the avian liver. Experientia 32:737–740
Püschel GP (2004) Control of hepatocyte metabolism by sympathetic and parasympathetic hepatic nerves. Anat Rec 280A:854–867
Quadro L, Blaner WS, Salchow DJ, Vogel S, Piantedosi R, Gouras P, Freeman S, Cosma MP, Colantuoni V, Gottesman ME (1999) Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein. EMBO J 18:4633–4644
Quadro L, Hamberger L, Colantuoni V, Gottesman ME, Blaner WS (2003) Understanding the physiological role of retinol-binding protein in vitamin A metabolism using transgenic and knockout mouse models. Mol Aspect Med 24:421–430
Quadro L, Blaner WS, Hamberger L, Novikoff PM, Vogel S, Piantedosi R, Gottesman ME, Colantuoni V (2004) The role of extrahepatic retinol binding protein in the mobilization of retinoid stores. J Lipid Res 45:1975–1982
Quan TE, Cowper S, Wu S-P, Bockenstedt LK, Bucala R (2004) Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int J Biochem Cell Biol 36:598–606
Radaeva S, Wang L, Radaev S, Jeong WI, Park O, Gao B (2007) Retinoic acid signaling sensitizes hepatic stellate cells to NK cell killing via upregulation of NK cell activating ligand RAE1. Am J Physiol Gastrointest Liver Physiol 293:G809–G816
Raddatz D, Henneken M, Armbrust T, Ramadori G (1996) Subcellular distribution of glucocorticoid receptor in cultured rat and human liver-derived cells and cell lines: influence of dexamethasone. Hepatology 24:928–933
Ramadori G (1991) The stellate cell (Ito-cell, fat-storing cell, lipocyte, perisinusoidal cell) of the liver. New insights into pathophysiology of an intriguing cell. Virchows Arch [B] 61:147–158
Ramadori G, Saile B (2002) Mesenchymal cells in the liver-one cell type or two? Liver 22:283–294
Ramadori G, Knittel T, Schwogler S, Bieber F, Rieder H, Meyer zum Buschenfelde KH (1991) Dexamethasone modulates α 2-macroglobulin and apolipoprotein E gene expression in cultured rat liver fat-storing (Ito) cells. Hepatology 14:875–882
Ramm GA, Britton RS, O’Neill R, Blaner WS, Bacon BR (1995) Vitamin A-poor lipocytes: a novel desmin-negative lipocyte subpopulation, which can be activated to myofibroblasts. Am J Physiol Gastrointest Liver Physiol 269:G532–G541
Ramm GA, Nair VG, Bridle KR, Shepherd RW, Crawford DHG (1998) Contribution of hepatic parenchymal and nonparenchymal cells to hepatic fibrogenesis in biliary atresia. Am J Pathol 153:527–535
Randolph RK, Winkler KE, Ross AC (1991) Fatty acyl CoA-dependent and -independent retinol esterification by rat liver and lactating mammary gland microsomes. Arch Biochem Biophys 288:500–508
Rashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E, Alexander G, Huang-Doran I, Griffin J, Ahrlund-Richter L, Skepper J, Semple R, Weber A, Komas DA, Vaillier L (2010) Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest 120:3127–3130
Ratziu V, Lalazar A, Wong L, Dang Q, Collins C, Shaulian E, Jensen S, Friedman SL (1998) Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis. Proc Natl Acad Sci USA 95:9500–9505
Redlich CA, Grauer JN, Van Bennekum AM, Clever SL, Ponn RB, Blaner WS (1996) Characterization of carotenoid, vitamin A, and α-tocopheral levels in human lung tissue and pulmonary macrophages. Am J Respir Crit Care Med 154:1436–1443
Reid LM, Fiorino AS, Sigal SH, Brill S, Holst PA (1992) Extracellular matrix gradients in the space of Disse: relevance to liver biology. Hepatology 15:1198–1203
Reif S, Lang A, Lindquist JN, Yata Y, Gäbele E, Scanga A, Brenner DA, Rippe RA (2003) The role of focal adhesion kinase-phosphatidylinositol 3-kinase-Akt signaling in hepatic stellate cell proliferation and type I collagen expression. J Biol Chem 278:8083–8090
Reilly FD, McCuskey PA, McCuskey RS (1978) Intrahepatic distribution of nerves in the rat. Anat Rec 191:55–67
Reimann T, Hempel U, Krautwald S, Axmann A, Scheibe R, Seidel D, Wenzel K-W (1997) Transforming growth factor-b1 induces activation of Ras, Raf-1, MEK and MAPK in rat hepatic stellate cells. FEBS Lett 403:57–60
Rhodin J (1964) American Association of Anatomists Seventy-Seventh Session University of Colorado School of Medicine March 31, April 1, 2, 3, 1964. Anat Rec 148:326
Riordan SM, Skinner N, Nagree A, McCallum H, McIver CJ, Kurtovic J, Hamilton JA, Bengmark S, Williams R, Visvanathan K (2003) Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis. Hepatology 37:1154–1164
Rippe RA, Brenner DA (2004) From quiescence to activation: gene regulation in hepatic stellate cells. Gastroenterology 127:1260–1262
Robenek H, Hofnagel O, Buers I, Robenek MJ, Troyer D, Severs NJ (2006) Adipophilin-enriched domains in the ER membrane are sites of lipid droplet biogenesis. J Cell Sci 119:4215–4224
Rockey DC (1995) Characterization of endothelin receptors mediating rat hepatic stellate cell contraction. Biochem Biophys Res Commun 207:725–731
Rockey DC (2003) Vascular mediators in the injured liver. Hepatology 37:4–12
Rockey DC, Weisiger RA (1996) Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance. Hepatology 24:233–240
Rockey DC, Maher JJ, Jarnagin WR, Gabbiani G, Friedman SL (1992) Inhibition of rat hepatic lipocyte activation in culture by interferon-γ. Hepatology 16:776–784
Rodahl K (1949a) Toxicity of polar bear liver. Nature (London) 164:530–531
Rodahl K (1949b) Vitamin sources in Arctic regions. Nor Polarinst Skr 91:1–64
Rodahl K, Moore T (1943) The vitamin A content and toxicity of bear and seal liver. Biochem J 37:166–168
Rojkind M, Greenwel P (1994) The extracellular matrix of the liver. In: Arias IA, Boyer JL, Fausto N, Jakoby WB, Schachter DA, Shafritz DA (eds) The liver: biology and pathobiology. Raven, New York, pp 843–868
Rojkind M, Novikoff PM, Greenwel P, Rubin J, Rojas-Valencia L, de Carvalho AC, Stockert R, Spray D, Hertzberg EL, Wolkoff AW (1995) Characterization and functional studies on rat liver fat-storing cell line and freshly isolated hepatocyte coculture system. Am J Pathol 146:1508–1519
Rombouts K, Niki T, Wielant A, Hellemans K, Schuppan D, Kormoss N, Geerts A (2001) Effect of aldosterone on collagen steady state levels in primary and subcultured rat hepatic stellate cells. J Hepatol 34:230–238
Rombouts K, Knittel T, Machesky L, Braet F, Wielant A, Hellemans K, De Bleser P, Gelman I, Ramadori G, Albert A (2002) Actin filament formation, reorganization and migration are impaired in hepatic stellate cells under influence of trichostatin A, a histone deacetylase inhibitor. J Hepatol 37:788–796
Rosales C, O’Brien V, Kornberg L, Juliano R (1995) Signal transduction by cell adhesion receptors. Biochim Biophys Acta 1242:77–98
Rosette C, Karin M (1995) Cytoskeletal control of gene expression: depolymerization of microtubules activates NF-κB. J Cell Biol 128:1111–1119
Roskelley CD, Srebrow A, Bissell MJ (1995) A hierarchy of ECM-mediated signaling regulates tissue-specific gene expression. Curr Opin Cell Biol 7:736–747
Ross AC (1982) Retinol esterification by rat liver microsomes. J Biol Chem 257:2453–2459
Ross AC (1993) Cellular metabolism and activation of retinoids: roles of cellular retinoid-binding proteins. FASEB J 7:317–327
Ross AC (1999) Mutations in the gene encoding retinol binding protein and retinol deficiency: is there compensation by retinyl esters and retinoic acid? Am J Clin Nutr 69:829–830
Ross AC (2004) On the sources of retinoic acid in the lung: understanding the local conversion of retinol to retinoic acid. Am J Physiol Lung Cell Mol Physiol 286:L247–L248
Rothe P (1882) Ueber die Sternzellen der Leber. Inaug-Dissertation, München
Rubin E, Florman AL, Degnan T, Diaz J (1970) Hepatic injury in chronic hypervitaminosis A. Am J Dis Child 119:132–138
Rozga J, Demetriou AA (1995) Artificial liver: evolution and future perspectives. ASAIO J 41:831–837
Ruiz A, Winston A, Lim YH, Gilbert BA, Rando RR, Bok D (1999) Molecular and biochemical characterization of lecithin retinol acyltransferase. J Biol Chem 274:3834–3841
Russo FP, Alison MR, Bigger BW, Amofah E, Florou A, Amin F, Bou-Gharios G, Jeffery R, Iredale JP, Forbes SJ (2006) The bone marrow functionally contributes to liver fibrosis. Gastroenterology 130:1807–1821
Saari JC, Bredberg L, Garwin GG (1982) Identification of the endogenous retinoids associated with three cellular retinoid-binding proteins from bovine retina and retinal pigment epithelium. J Biol Chem 257:13329–13333
Sakakibara K, Saito M, Umeda M, Enaka K, Tsukada Y (1976) Native collagen formation by liver parenchymal cells in culture. Nature 262:316–318
Sancho-Bru P, Bataller R, Colmenero J, Gasull X, Moreno M, Arroyo V, Brenner DA, Ginès P (2006) Norepinephrine induces calcium spikes and proinflammatory actions in human hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 291:G877–G884
Sandgren ME, Bronnegard M, DeLuca HF (1991) Tissue distribution of the 1,25-dihydroxyvitamin D3 receptor in the male rat. Biochem Biophys Res Commun 181:611–616
Sario AD, Bendia E, Macarri G, Candelaresi C, Taffetani S, Marzioni M, Omenetti A, De Minicis S, Trozzi L, Benedetti A (2004) The anti-fibrotic effect of pirfenidone in rat liver fibrosis is mediated by downregulation of procollagen a1(I), TIMP-1 and MMP-2. Dig Liver Dis 36:744–751
Sato M, Senoo H (1998) Morphological regulation of cultured hepatic stellate cells by extracellular matrix through intracellular signaling. Connect Tissue 30:219–224
Sato T, Kato R, Tyson CA (1995) Regulation of differentiated phenotype of rat hepatic lipocytes by retinoids in primary culture. Exp Cell Res 217:72–83
Sato M, Imai K, Kojima N, Miura M, Senoo H (1997) Long cellular processes of hepatic stellate cells cultured on or in type I collagen gel. In: Wisse E, Knook DL, Balabaud C (eds) Cells of the hepatic sinusoid, vol 6. Kupffer Cell Foundation, Leiden, pp 85–89
Sato M, Kojima N, Miura M, Imai K, Senoo H (1998) Induction of cellular processes containing collagenase and retinoid by integrin-binding to interstitial collagen in hepatic stellate cell culture. Cell Biol Int 22:115–125
Sato M, Kojima N, Miura M, Imai K, Senoo H (1999) Intracellular signaling for process elongation in cultured hepatic stellate cells on type I collagen gel. In: Wisse E, Knook DL, de Zanger R, Fraser R (eds) Cells of the hepatic sinusoid, vol 7. Kupffer Cell Foundation, Leiden, pp 32–33
Sato M, Miura M, Kojima N, Higashi N, Imai K, Sato T, Wold HL, Moskaug JØ, Blomhoff R, Wake K, Roos N, Berg T, Norum KR, Senoo H (2001a) Nuclear deviation in hepatic parenchymal cells on sinusoidal surface in arctic animals. Cell Struct Funct 26:71–77
Sato M, Sato T, Kojima N, Miura M, Imai K, Wang DR, Senoo H (2001b) Induction of cellular process elongation mediated by microtubule-associated protein 2 in hepatic stellate cells cultured on type I collagen gel. In: Wisse E, Knook DL, de Zanger R, Arthur MJP (eds) Cells of the hepatic sinusoid, vol 8. Kupffer Cell Foundation, Leiden, pp 205–206
Sato M, Suzuki S, Senoo H (2003) Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct 28:105–112
Sato M, Sato T, Kojima N, Imai K, Higashi N, Wang DR, Senoo H (2004) Three-dimensional structure of extracellular matrix regulates gene expression in cultured stellate cells to induce process elongation. Comp Hepatol 3(Suppl 1):S4
Sato Y, Murase K, Kato J, Kobune M, Sato T, Kawano Y, Takimoto R, Takada K, Miyanishi K, Matsunaga T, Takayama T, Niitsu Y (2008) Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol 26:431–442
Sauvant P, Sapin V, Alexandre-Gouabau M-C, Dodeman I, Delpal S, Quadro L, Partier A, Abergel A, Colantuoni V, Rock E, Azaïs-Braesco V (2001) Retinol mobilization from cultured rat hepatic stellate cells does not require retinol binding protein synthesis and secretion. Int J Biochem Cell Biol 33:1000–1012
Schieferdecker HK, Pestel S, Rothermel E, Püschel GP, Götze O, Jungermann K (1998) Stimulation by anaphylatoxin C5a of glycogen phosphorylase in rat hepatocytes via prostanoid release from hepatic stellate cells but not sinusoidal endothelial cells. FEBS Lett 434:245–250
Schnack H, Stockinger L, Wewalka F (1966) Die Bindegewebeszellen des Dissesch en Raumes in der menschlichten Leber bei Normafaellen und pathologischen Zustaenden. Wien klin Wochschr 78:715–724
Schneider E, Schmid-Kotsas A, Zhao J, Weidenbach H, Schmid RM, Menke A, Adler G, Waltenberger J, Grünert A, Bachem MG (2001) Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells. Am J Physiol Cell Physiol 281:G532–G543
Schneiderhan W, Schmid-Kotsas A, Zhao J, Grünert A, Nüssler A, Weidenbach H, Menke A, Schmid RM, Adler G, Bachem MG (2001) Oxidized low-density lipoproteins bind to the scavenger receptor, CD36, of hepatic stellate cells and stimulate extracellular matrix synthesis. Hepatology 34:729–737
Schwabe RF, Seki E, Brenner DA (2006) Toll-like receptor signaling in the liver. Gastroenterology 130:1886–1900
Schwögler S, Odenthal M, Knittel T, Meyer zum Büschenfelde K-H, Ramadori G (1992) Fat-storing cells of the rat liver synthesize and secrete C1-esterase inhibitor; modulation by cytokines. Hepatology 16:794–802
Seeliger MW, Biesalski HK, Wissinger B, Gollnick H, Gielen S, Frank J, Beck S, Zrenner E (1999) Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis. Invest Ophthalmol Vis Sci 40:3–11
Seifert WF, Bosma A, Brouwer A, Hendriks HFJ, Roholl PJM, van Leeuwen REW, van Thiel-DeRuiter GCF, Seifert-Bock I, Knook DL (1994a) Vitamin A deficiency potentiates carbon tetrachloride-induced liver fibrosis in rats. Hepatology 19:193–201
Seifert WF, Roholl PJ, Blauw B, van der Ham F, van Thiel-De Ruiter CF, Seifert-Bock I, Bosma A, Knook DL, Brouwer A (1994b) Fat-storing cells and myofibroblasts are involved in the initial phase of carbon tetrachloride-induced hepatic fibrosis in BN/BiRij rats. Int J Exp Pathol 75:131–146
Seki E, De Minicis S, Österreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF (2007) TLR4 enhances TGF-β signaling and hepatic fibrosis. Nat Med 13:1324–1332
Senoo H (2000) Digestion, Metabolism. In: Krinke GJ (ed) The digital handbook of experimental laboratory animals: the rat. Academic, London, pp 359–383
Senoo H (2004) Structure and function of hepatic stellate cells. Med Electron Microsc 37:3–15
Senoo H (2007a) Stellate cell-endothelial cell interactions. In: Aird WC (ed) Endothelial biomedicine. Cambridge University Press, Cambridge, pp 616–619
Senoo H (2007b) Vitamin A-storing cell (stellate cell) system. In: Loessing IT (ed) Vitamin A: new research. Nova Science, New York, pp 59–70
Senoo H (2014) The stellate cell (vitamin A-storing cell) system. Nova Science, New York, pp 1–245
Senoo H, Hata R (1993a) Tissue formation and extracellular matrix system—cellular devices for adhesion to extracellular matrix. Tissue Cult Res Commun 12:237–245
Senoo H, Hata R (1993b) Isolation of perisinusoidal stellate cells (vitamin A-storing cells, fat-storing cells) of the rat liver. Connect Tissue 25:129–137
Senoo H, Hata R (1994a) Extracellular matrix regulates and l-ascorbic acid 2-phosphate further modulates morphology, proliferation, and collagen synthesis of the perisinusoidal stellate cells. Biochem Biophys Res Commun 200:999–1006
Senoo H, Hata R (1994b) Extracellular matrix regulates cell morphology, proliferation, and tissue formation. Acta Anat Nippon 69:719–733
Senoo H, Hata R (1995) Regulation of morphology, proliferation, and collagen metabolism of perisinusoidal stellate cells by extracellular matrix. In: Wisse E, Knook DL, Wake K (eds) Cells of the hepatic sinusoid, vol 5. Kupffer Cell Foundation, Leiden, pp 430–431
Senoo H, Wake K (1985) Suppression of experimental hepatic fibrosis by administration of vitamin A. Lab Invest 52:182–194
Senoo H, Wake K (1988) Histochemical method for detection of vitamin A. Vitamins 59:465–469
Senoo H, Hata R, Nagai Y, Wake K (1984) Stellate cells (vitamin A-storing cells) are the primary site of collagen synthesis in non-parenchymal cells in the liver. Biomed Res 5:451–458
Senoo H, Tsukada Y, Sato T, Hata RI (1989) Co-culture of fibroblasts and hepatic parenchymal cells induces metabolic changes and formation of a three-dimensional structure. Cell Biol Int Rep 13:197–206
Senoo H, Stang E, Nilsson A, Kindberg GM, Berg T, Roos N, Norum KR, Blomhoff R (1990) Internalization of retinol-binding protein in parenchymal and stellate cells of rat liver. J Lipid Res 31:1229–1239
Senoo H, Hata R, Wake K, Nagai Y (1991) Isolation and serum free culture of stellate cells. In: Wisse E, Knook DL, McCuskey RS (eds) Cells of the hepatic sinusoid, vol 3. Kupffer Cell Foundation, Leiden, pp 259–262
Senoo H, Smeland S, Malaba L, Bjerknes T, Stang E, Roos N, Berg T, Norum KR, Blomhoff R (1993) Transfer of retinol-binding protein from HepG2 human hepatoma cells to cocultured rat stellate cells. Proc Natl Acad Sci USA 90:3616–3620
Senoo H, Imai K, Sato M, Kojima N, Miura M, Hata R (1996) Three-dimensional structure of extracellular matrix reversibly regulates morphology, proliferation and collagen metabolism of perisinusoidal stellate cells (vitamin A-storing cells). Cell Biol Int 20:501–512
Senoo H, Sato M, Imai K (1997) Hepatic stellate cells—from the viewpoint of retinoid handling and function of the extracellular matrix. Acta Anat Nippon 72:79–94
Senoo H, Imai K, Matano Y, Sato M (1998) Molecular mechanisms in the reversible regulation of morphology, proliferation and collagen metabolism in hepatic stellate cells by the three-dimensional structure of the extracellular matrix. J Gastroenterol Hepatol 13:S19–S32
Senoo H, Imai K, Wake K, Wold HL, Moskaug JØ, Kojima N, Matano Y, Miura M, Sato M, Roos N, Berg T, Langvatn R, Norum KR, Blomhoff R (1999) Vitamin A-storing system in mammals and birds in Arctic area—a study in the Svalbard archipelago. In: Wisse E, Knook DL, de Zanger R, Fraser R (eds) Cells of the hepatic sinusoid, vol 7. Kupffer Cell Foundation, Leiden, pp 34–35
Senoo H, Wake K, Wold HL, Higashi N, Imai K, Moskaug JØ, Kojima N, Miura M, Sato T, Sato M, Roos N, Berg T, Norum KR, Blomhoff R (2004) Decreased capacity for vitamin A storage in hepatic stellate cells in arctic animals. Comp Hepatol 3(Suppl 1):S18
Senoo H, Kojima N, Sato M (2007) Vitamin A-storing cells (stellate cells). Vitam Horm 75:131–159
Senoo H, Yoshikawa K, Morii M, Miura M, Imai K, Mezaki Y (2010) Hepatic stellate cell (vitamin A-storing cell) and its relative–past, present, and future. Cell Biol Int 34:1247–1272 (editor’s special 70th birthday edition)
Senoo H, Mezaki Y, Miura M, Sanada C, Umezono-Hanata Y, Morii M, Imai K, Fujiwara M (2011a) Hepatic stellate cell (vitamin A-storing cell) and its relative. Recent Res Dev Nutr 8:129–147 (editor Shankar Pandalai, ISBN: 978-81-308-0468-2)
Senoo H, Yoshikawa K, Morii M, Fujiwara M, Besshi K, Mezaki Y (2011b) Regulation of vitamin A homeostasis by the stellate cell (vitamin A-storing cell) system. In: Lucas P (ed) Vitamin A: nutrition, side effects and supplements nutrition and diet research progress. Scott ebook Nova Science, New York, pp 47–74
Senoo H, Imai K, Mezaki Y, Miura M, Morii M, Fujiwara M, Blomhoff R (2012) Accumulation of vitamin A in the hepatic stellate cell of arctic top predators. Anat Rec 295:1660–1668
Senoo H, Mezaki Y, Morii M, Hebiguchi T, Miura M, Imai K (2013) Uptake and storage of vitamin A as lipid droplets in the cytoplasm in cells in lamina propria mucosae of rat intestine. Cell Biol Int 37:1171–1180
Servetnick DA, Brasaemle DL, Gruia-Gray J, Kimmel AR, Wolff J, Londos C (1995) Perilipins are associated with cholesteryl ester droplets in steroidogenic adrenal cortical and Leydig cells. J Biol Chem 270:16970–16973
Severn CB (1971) A morphological study of the development of the human liver. I. Development of the hepatic diverticulum. Am J Anat 131:133–158
Severn CB (1972) A morphological study of the development of the human liver. II. Establishment of liver parenchyma, extrahepatic ducts and associated venous channels. Am J Anat 133:85–108
She H, Xiong S, Hazra S, Tsukamoto H (2005) Adipogenic transcriptional regulation of hepatic stellate cells. J Biol Chem 280:4959–4967
Shidoji Y, Muto Y (1977) Vitamin A transport in plasma of the non-mammalian vertebrates: isolation and partial characterization of piscine retinol-binding protein. J Lipid Res 18:679–691
Shimada T, Ross AC, Muccio DD, Brouillette WJ, Shealy YF (1997) Regulation of hepatic lecithin:retinol acyltransferase activity by retinoic acid receptor-selective retinoids. Arch Biochem Biophys 344:220–227
Shimizu I (2003) Impact of oestrogens on the progression of liver disease. Liver Int 23:63–69
Shimizu I, Mizobuchi Y, Yasuda M, Shiba M, Ma YR, Horie T, Liu F, Ito S (1999) Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro. Gut 44:127–136
Shimizu K, Kobayashi M, Tahara J, Shiratori K (2005) Cytokines and peroxisome proliferator-activated receptor γ ligand regulate phagocytosis by pancreatic stellate cells. Gastroenterology 128:2105–2118
Shin YC (1981) Some observations on perisinusoidal lipocyte (Ito cell) of Carassius auratus liver as revealed by electron microscopy. Acta Anat Nippon 56:133–144
Shiota G, Tsuchiya H, Hoshikawa Y (2006) The liver as a target organ of retinoids. Hepatol Res 36:248–254
Sigal SH, Brill S, Fiorino AS, Reid LM (1992) The liver as a stem cell and lineage system. Am J Physiol Gastrointest Liver Physiol 263:G139–G148
Skaare JU, Bernhoft A, Wiig Ø, Norum KR, Haug E, Eide DM, Derocher AE (2001) Relationship between plasma levels of organochlorines, retinol and thyroid hormones from polar bears (Ursus maritimus) at Svalbard. J Toxicol Environ Health 62:227–241
Smart DE, Vincent KJ, Arthur MJP, Eickelberg O, Castellazzi M, Mann DA (2001) JunD regulates transcription of the tissue inhibitor of metalloproteinases-1 and interleukin-6 genes in activated hepatic stellate cells. J Biol Chem 276:24414–24421
Smedsrød B, Le Couteur D, Ikejima K, Jaeschke H, Kawada N, Naito M, Knolle P, Nagy L, Senoo H, Vidal-Vanaclocha F, Yamaguchi N (2009) Hepatic sinusoidal cells in health and disease: update from the 14th International Symposium. Liver Int 29:491–501
Smeland S, Bjerknes T, Malaba L, Eskild W, Norum KR, Blomhoff R (1995) Tissue distribution of the receptor for plasma retinol-binding protein. Biochem J 305:419–424
Smith FR, Goodman DS (1971) The effects of diseases of the liver, thyroid, and kidneys on the transport of vitamin A in human plasma. J Clin Invest 50:2426–2436
Smith JE, Goodman DW (1979) Retinol-binding protein and the regulation of vitamin A transport. Fed Proc 38:2504–2509
Sorrell JM, Caplan AI (2004) Fibroblast heterogeneity: more than skin deep. J Cell Sci 117:667–675
Spit BJ (1983) Induction of lipid droplets in fibroblasts of the hamster lung by a diet high in vitamin A. Exp Lung Res 4:247–257
Staatz WD, Fok KF, Zutter MM, Adams SP, Rodriguez BA, Santoro SA (1991) Identification of a tetrapeptide recognition sequence for the α2β1 integrin in collagen. J Biol Chem 266:7363–7367
Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E, Fritsche A, Häring H-U (2007) High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care 30:1173–1178
Steffan A-M, Gendrault J-L, McCuskey RS, McCuskey PA, Kirn A (1986) Phagocytosis, an unrecognized property of murine endothelial liver cells. Hepatology 6:830–836
Steiniger B, Klempnauer J, Wonigeit K (1984) Phenotype and histological distribution of interstitial dendritic cells in the rat pancreas, liver, heart, and kidney. Transplantation 38:169–175
Stewart SF, Day CP (2003) The management of alcoholic liver disease. J Hepatol 38:S2–S13
Stockinger L (1967) Anat Anz (verh Anat Ges) 120:545
Strain AJ (1999) Ex vivo liver cell morphogenesis: one step nearer to the bioartificial liver? Hepatology 29:288–290
Straub BK, Stoeffel P, Heid H, Zimbelmann R, Schirmacher P (2008) Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology 47:1936–1946
Sundaram M, Sivaprasadarao A, DeSousa MM, Findlay JBC (1998) The transfer of retinol from serum retinol-binding protein to cellular retinol-binding protein is mediated by a membrane receptor. J Biol Chem 273:3336–3342
Sung CK, She H, Xiong S, Tsukamoto H (2004) Tumor necrosis factor-α inhibits peroxisome proliferator-activated receptor γ activity at a posttranslational level in hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 286:G722–G729
Suskind DL, Muench MO (2004) Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver: CD34+ cytokeratin 7/8+ cells express markers for stellate cells. J Hepatol 40:261–268
Suzuki K (1958) A silver impregnation method in histology. Takeda Pharm Ind Osaka. Pharmacutical company, Takeda pp 310–320
Suzuki L (1963) Proc Gen Ass Med Congr, 16th, Osaka, IV 13
Svegliati-Baroni G, Ridolfi F, Hannivoort R, Saccomanno S, Homan M, De Minicis S, Jansen PL, Candelaresi C, Benedetti A, Moshage H (2005) Bile acids induce hepatic stellate cell proliferation via activation of the epidermal growth factor receptor. Gastroenterology 128:1042–1055
Tabb MM, Sun A, Zhou C, Grun F, Errandi J, Romero K, Pham H, Inoue S, Mallick S, Lin M, Forman BM, Blumberg B (2003) Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem 278:43919–43927
Tahashi Y, Matsuzaki K, Date M, Yoshida K, Furukawa F, Sugano Y, Matsushita M, Himeno Y, Inagaki Y, Inoue K (2002) Differential regulation of TGF-β signal in hepatic stellate cells between acute and chronic rat liver injury. Hepatology 35:49–61
Taimr P, Higuchi H, Kocova E, Rippe RA, Friedman SL, Gores GJ (2003) Activated stellate cells express the TRAIL receptor-2/death receptor-5 and undergo TRAIL-mediated apoptosis. Hepatology 37:87–95
Takada Y, Wayner EA, Carter WG, Hemler ME (1988) Extracellular matrix receptors, ECMRII and ECMRI, for collagen and fibronectin correspond to VLA-2 and VLA-3 in the VLA family of heterodimers. J Cell Biochem 37:385–393
Takeuchi T, Sasaki M, Shiraishi Y, Akasaka M, Otsuka Y (1967) J jpn Soc RES 7:127
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Takase S, Leo MA, Nouchi T, Lieber C (1988) Desmin distinguishes cultured fat-storing cells from myofibroblasts, smooth muscle cells and fibroblasts in the rat. J Hepatol 6:267–276
Tanaka K (1955) Histochemical studies of vitamin A. J Kyoto Prefect Med Univ 58:333–377
Tateno C, Yoshizato K (1996) Long-term cultivation of adult rat hepatocytes that undergo multiple cell divisions and express normal parenchymal phenotypes. Am J Pathol 148:383–392
Tauchi-Sato K, Ozeki S, Houjou T, Taguchi R, Fujimoto T (2002) The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition. J Biol Chem 277:44507–44512
Théret N, Lehti K, Musso O, Clément B (1999) MMP2 activation by collagen I and concanavalin A in cultured human hepatic stellate cells. Hepatology 30:462–468
Tomasek JJ, Hay ED (1984) Analysis of the role of microfilaments and microtubules in acquisition of bipolarity and elongation of fibroblasts in hydrated collagen gels. J Cell Biol 99:536–549
Tomasek JJ, Hay ED, Fujiwara K (1982) Collagen modulates cell shape and cytoskeleton of embryonic corneal and fibroma fibroblasts: distribution of actin, α-actinin, and myosin. Dev Biol 92:107–122
Tran-Thi T, Kawada N, Decker K (1993) Regulation of endothelin-1 action on the perfused rat liver. FEBS Lett 318:353–357
Trim N, Morgan S, Evans M, Issa R, Fine D, Afford S, Wilkins B, Iredale J (2000) Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation. Am J Pathol 156:1235–1243
Trøen G, Nilsson A, Norum KR, Blomhoff R (1994) Characterization of liver stellate cell retinyl ester storage. Biochem J 300:793–798
Tsuiki E, Fujita A, Ohsaki Y, Cheng J, Irie T, Yoshikawa K, Senoo H, Mishima K, Kitaoka T, Fujimoto T (2007) All-trans-retinol generated by rhodopsin photobleaching induces rapid recruitment of TIP47 to lipid droplets in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 48:2858–2867
Tsukamoto H (2005) Fat paradox in liver disease. Keio J Med 54:190–192
Tsutsumi M, Takada A, Takase S (1987) Characterization of desmin-positive rat liver sinusoidal cells. Hepatology 7:277–284
Uchio K, Tuchweber B, Manabe N, Gabbiani G, Rosenbaum J, Desmoulière A (2002) Cellular retinol-binding protein-1 expression and modulation during in vivo and in vitro myofibroblastic differentiation of rat hepatic stellate cells and portal fibroblasts. Lab Invest 82:619–628
Ueno T, Bioulac-Sage P, Balabaud C, Rosenbaum J (2004) Innervation of the sinusoidal wall: regulation of the sinusoidal diameter. Anat Rec Part A 280A:868–873
Uyama N, Shimahara Y, Kawada N, Seki S, Okuyama H, Iimuro Y, Yamaoka Y (2002) Regulation of cultured rat hepatocyte proliferation by stellate cells. J Hepatol 36:590–599
Varela-Rey M, Montiel-Duarte C, Osés-Prieto JA, López-Zabalza MJ, Jaffrèzou JP, Rojkind M, Iraburu MJ (2002) p38 MAPK mediates the regulation of a1(I) procollagen mRNA levels by TNF-a and TGF-b in a cell line of rat hepatic stellate cells. FEBS Lett 528:133–138
Varet KS, Grompe M (2008) Generation and regeneration of cells of the liver and pancreas. Science 322:1490–1494
Viñas O, Bataller R, Sacho-Bru P, Gines P, Berenguer C, Enrich C, Nicolás JM, Ercilla G, Gallart T, Vives J, Arroyo V, Rodés J (2003) Human hepatic stellate cells show features of antigen-presenting cells and stimulate lymphocyte proliferation. Hepatology 38:919–929
Vincent KJ, Jones E, Arthur MJP, Smart DE, Trim J, Wright MC, Mann DA (2001) Regulation of E-box DNA binding during in vivo and in vitro activation of rat and human hepatic stellate cells. Gut 49:713–719
Vogel W, Gish GD, Alves F, Pawson T (1997) The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell 1:13–23
Vogel S, Mendelsohn CL, Mertz JR, Piantedosi R, Waldburger C, Gottesman ME, Blaner WS (2001) Characterization of a new member of the fatty acid-binding protein family that binds all-trans-retinol. J Biol Chem 276:1353–1360
Vollmar B, Heckmann C, Richter S, Menger MD (2002a) High, but not low, dietary retinoids aggravate manifestation of rat liver fibrosis. J Gastroenterol Hepatol 17:791–799
Vollmar B, Pradrarutti S, Richter S, Menger MD (2002b) In vivo quantification of ageing changes in the rat liver from early juvenile to senescent life. Liver 22:330–341
Vyalov SL, Gabbiani G, Kapanci Y (1993) Rat alveolar myofibroblasts acquire alpha-smooth muscle actin expression during bleomycin-induced pulmonary fibrosis. Am J Pathol 143:1754–1765
Wake K (1964) Distribution of vitamin A in the liver. In: Miyake M (ed) Proceedings of 5th annual meeting of Japanese histochemical association, pp 103–106
Wake K (1971) “Sternzellen” in the liver: perisinusoidal cells with special reference to storage of vitamin A. Am J Anat 132:429–462
Wake K (1973) Cytochemistry of the lipid droplets containing vitamin A in the liver. In: Wisse E, Daems WTh, Molenaar I, van Duijn P (eds) Electron microscopy and cytochemistry. North-Holland, Amsterdam, pp 279–282
Wake K (1974) Development of vitamin A-rich lipid droplets in multivesicular bodies of rat liver stellate cells. J Cell Biol 63:683–691
Wake K (1975a) One hundred years of the stellate cells of von Kupffer. In: Proceedings of 10th international congress of anatomists, August 25–30
Wake K (1975b) Lysosomes in the hypervitaminosis A rat liver, with special reference to storage of vitamin A in the perisinusoidal stellate cells. Recent Adv RES Res 15:83–92
Wake K (1975c) The stellate cell of the liver. Kagaku (Science) 45:33–42
Wake K (1976) Structure of the sinusoidal wall in the hypervitaminosis A rat liver. J Electron Microsc 25:218
Wake K (1978) Kupffer's original article of discovery of the stellate cell in liver. Acta Anat Nippon 53:368–372
Wake K (1980a) Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 66:303–353
Wake K (1980b) So-called Kupffer cells and hepatic stellate cells. Saibo (Cell) 12:189–198
Wake K (1982) The Sternzellen of von Kupffer-after 106 years. In: Knook DL, Wisse E (eds) Sinusoidal liver cells. Elsevier Biomed, Amsterdam, pp 1–12
Wake K (1995) Structure of the sinusoidal wall in the liver. In: Wisse E, Knook DL, Wake K (eds) Cells of the hepatic sinusoid, vol 5. Kupffer Cell Foundation, Leiden, pp 241–246
Wake K (1997a) Cells in and around the hepatic sinusoid: past, present and future. In: Motta PM (ed) Recent advances in microscopy of cells, tissues and organs. Antonio Delfino, Rome, pp 421–428
Wake K (1997b) One hundred years of sinusoidal cells in the liver. Acta Anat Nippon 72:407–423
Wake K (1998) Hepatic stellate cells. Connect Tissue 30:245–246
Wake K (2006) Hepatic stellate cells: three-dimensional structure, localization, heterogeneity and development. Proc Jpn Acad Ser B 82:155–164
Wake K (2009) Browcz’s phagocytic cells and Kupffer’s ‘so-called stellate cells’. Acta Anat Nippon 84:17–21
Wake K, Senoo H (1986) Morphological aspects of the differentiation of stellate cell line in the vertebrates. In: Kirn A, Knook DL, Wisse E (eds) Cells of the hepatic sinusoid, vol 1. Leiden, pp 215–220
Wake K, Motomatsu K, Senoo H, Masuda A, Adachi E (1986) Improved Kupffer’s gold chloride method for demonstrating the stellate cells storing retinol (vitamin A) in the liver and extrahepatic organs of vertebrates. Stain Technol 61:193–200
Wake K, Motomatsu K, Senoo H (1987) Stellate cells storing retinol in the liver of adult lamprey, Lampetra japonica. Cell Tissue Res 249:289–299
Wang SC, Ohata M, Schrum L, Rippe RA, Tsukamoto H (1998) Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J Biol Chem 273:302–308
Wang L, Tankersley LR, Tang M, Potter JJ, Mezey E (2002) Regulation of the murine α2(I) collagen promoter by retinoic acid and retinoid X receptors. Arch Biochem Biophys 401:262–270
Wang DR, Sato M, Li LN, Miura M, Kojima N, Senoo H (2003) Stimulation of pro-MMP-2 production and activation by native form of extracellular type I collagen in cultured hepatic stellate cells. Cell Struct Funct 28:505–513
Wang X, Tang X, Gong X, Albanis E, Friedman SL, Mao Z (2004a) Regulation of hepatic stellate cell activation and growth by transcription factor myocyte enhancer factor 2. Gastroenterology 127:1174–1188
Wang L, Tankersley LR, Tang M, Potter JJ, Mezey E (2004b) Regulation of α 2(I) collagen expression in stellate cells by retinoic acid and retinoid X receptors through interactions with their cofactors. Arch Biochem Biophys 428:92–98
Wang L, Potter JJ, Rennie-Tankersley L, Novitskiy G, Sipes J, Mezey E (2007) Effects of retinoic acid on the development of liver fibrosis produced by carbon tetrachloride in mice. Biochim Biophys Acta 1772:66–71
Wanless IR (1999) Physioanatomic considerations. In: Schiff ER, Sorrell MF, Maddrey WC (eds) Schiff’s diseases of the liver, 8th edn. Lippincott-Raven, Philadelphia, pp 3–37
Warren A, Bertolino P, Cogger VC, McLean AJ, Fraser R, Le Couteur DG (2005) Hepatic pseudocapillarization in aged mice. Exp Gerontol 40:807–812
Weinberger C, Hollenberg SM, Ong ES, Harmon JM, Brower ST, Cidlowski J, Thompson EB, Rosenfeld MG, Evans RM (1985a) Identification of human glucocorticoid receptor complementary DNA clones by epitope selection. Science 228:740–742
Weinberger C, Hollenberg SM, Rosenfeld MG, Evans RM (1985b) Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature 318:670–672
Weinberger C, Thompson CC, Ong ES, Lebo R, Gruol DJ, Evans RM (1986) The c-erb-A gene encodes a thyroid hormone receptor. Nature 324:641–646
Weiner FA, Giambrone M-A, Czaja MJ, Shah A, Annoni G, Takahashi S, Eghbali M, Zern MA (1990) Ito-cell gene expression and collagen regulation. Hepatology 11:111–117
Weiner FR, Blaner WS, Czaja MJ, Shah A, Geerts A (1992) Ito cell expression of a nuclear retinoic acid receptor. Hepatology 15:336–342
Wells RG, Crawford J (1998) Pancreatic stellate cells. The new stars of chronic pancreatitis? Gastroenterology 115:491–493
Wickert L, Abiaka M, Bolkenius U, Gressner AM (2004) Corticosteroids stimulate selectively transforming growth factor (TGF)-β receptor type III expression in transdifferentiating hepatic stellate cells. J Hepatol 40:69–76
Wieckowska A, McCullough AJ, Feldstein AE (2007) Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 46:582–589
Wiig Ø, Derocher AE, Cronin MM, Skaare JU (1998) Female pseudohermaphrodite polar bears at Svalbard. J Wildl Dis 34:792–796
Winau F, Hegasy G, Weiskirchen R, Weber S, Cassan C, Sieling PA, Modlin RL, Liblau RS, Gressner AM, Kaufmann S (2007) Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity 26:117–129
Wisse E (1970) An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoid. J Ultrastruct Res 31:125–150
Wisse E (1972) An ultrastructural characterization of the endothelial cell in the rat liver sinusoid under normal and various experimental conditions, as a contribution to the distinction between endothelial and Kupffer cells. J Ultrastruct Res 38:528–562
Wold HL, Wake K, Higashi N, Wang D-R, Kojima N, Imai K, Blomhoff R, Senoo H (2004) Vitamin A distribution and content in tissues of the lamprey (Lampetra japonica). Anat Rec 276A:134–142
Wolins NE, Rubin B, Brasaemle DL (2001) TIP47 associates with lipid droplets. J Biol Chem 276:5101–5108
Wood RL (1963) Evidence of species difference in the ultrastructure of the hepatic sinusoids. Z Zellforsch 58:679–692
Wolins NE, Brasaemle DL, Bickel PE (2006) A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett 580:5484–5491
Wright MC (2006) The impact of pregnane X receptor activation on liver fibrosis. Biochem Soc Trans 34:1119–1123
Wu H, Jia W, Bao Y, Lu J, Zhu J, Wang R, Chen Y, Xiang K (2008) Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 79:185–190
Xu J, Fu Y, Chen A (2003) Activation of peroxisome proliferator-activated receptor-γ contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth. Am J Physiol Gastrointest Liver Physiol 285:G20–G30
Yagmur E, Weiskirchen R, Gressner AM, Trautwein C, Tacke F (2007) Insulin resistance in liver cirrhosis is not associated with circulating retinol-binding protein 4. Diabetes Care 30:1168–1172
Yamada E (1982) Vitamin A storing cell. Method Enzymol 81:834–839
Yamada E, Hirosawa K (1976) The possible existence of a vitamin A-storing cell system. Cell Struct Funct 1:201–204
Yamada KM, Miyamoto S (1995) Integrin transmembrane signaling and cytoskeletal control. Curr Opin Cell Biol 7:681–689
Yamada M, Blaner WS, Soprano DR, Dixon JL, Kjeldbye HM, Goodman DS (1987) Biochemical characteristics of isolated rat liver stellate cells. Hepatology 7:1224–1229
Yamaguchi K, Yang L, McCall S, Huang J, Yu XX, Pandey SK, Bhanot S, Monia BP, Li YX, Diehl AM (2008) Diacylglycerol acyltranferase 1 anti-sense oligonucleotides reduce hepatic fibrosis in mice with nonalcoholic steatohepatitis. Hepatology 47:625–635
Yamamoto M, Enzan H (1975) Morphology and function of Ito cell (fat-storing cell) in the liver. Recent Adv RES Res 15:54–75
Yamamoto K, Ogawa K (1983) Fine structure and cytochemistry of lysosomes in the Ito cells of the rat liver. Cell Tissue Res 233:45–57
Yamamoto K, Ogawa K (1984) Freeze-replica study of lipid droplets in the Ito cells of rat liver. Anat Rec 210:415–420
Yamamoto M, Enzan H, Hara H, Iijima S (1978) Fluorescence and electron microscopic studies on the perivascular mesenchymal cells and fibroblasts after vitamin A administration. Acta Pathol Jpn 28:513–521
Yamauchi M, Potter JJ, Merzey E (1988) Characteristics of alcohol dehydrogenase in fat-storing (Ito) cells of rat liver. Gastroenterology 94:163–169
Yang C, Zeisberg M, Mosterman B, Sudhakar A, Yerramalla U, Holthaus K, Xu L, Eng F, Afdhal N, Kalluri R (2003) Liver fibrosis: insights into migration of hepatic stellate cells in response to extracellular matrix and growth factors. Gastroenterology 124:147–159
Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436:356–362
Yang L, Jung Y, Omenetti A, Witek RP, Choi S, Vandongen HM, Huang J, Alpini GD, Diehl AM (2008) Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers. Stem Cells 26:2104–2113
Yavrom S, Chen L, Xiong S, Wang J, Rippe RA, Tsukamoto H (2005) Peroxisome proliferator-activated receptor γ suppresses proximal α1(I) collagen promoter via inhibition of p300-facilitated NF-I binding to DNA in hepatic stellate cells. J Biol Chem 280:40650–40659
Yen CL, Monetti M, Burri BJ, Farese RV Jr (2005) The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. J Lipid Res 46:1502–1511
Yin C, Evason KJ, Maher JJ, Stainer YR (2012) The basic helix-loop-helix transcript factor, heart and neural crest derivatives expressed transcript 2, marks hepatic stellate cells in zebrafish: analysis of stellate cell entry into the developing liver. Hepatology 56:1958–1970
Ylikomi T, Bocquel MT, Berry M, Gronemeyer H, Chambon P (1992) Cooperation of proto-signals for nuclear accumulation of estrogen and progesterone receptors. EMBO J 11:3681–3694
Yokoi Y, Namihisa T, Kuroda H, Komatsu I, Miyazaki A, Watanabe S, Usui K (1984) Immunocytochemical detection of desmin in fat-storing cells (Ito cells). Hepatology 4:709–714
Yorifuji H, Hirosawa K, Yamada E (1980) Vitamin A storing cell in mouse urinary bladder—an autoradiographic study. J Electron Microsc 29:288
Youson JH, Sidon EW (1978) Lamprey biliary atresia: first model system for the human condition? Experientia 34:1084–1086
Yu MC, Chen CH, Liang X, Wang L, Gandhi CR, Fubg JJ, Lu L, Qian S (2004) Inhibition of T-cell responses by hepatic stellate cells via B7-H1-mediated T-cell apoptosis in mice. Hepatology 40:1312–1321
Zajicek G, Oren R, Weinreb M Jr (1985) The streaming liver. Liver 5:293–300
Zajicek G, Ariel I, Arber N (1988) The streaming liver III. Littoral cells accompany the streaming hepatocyte. Liver 8:213–218
Zaret KS (2001) Embryonic development of the liver. In: Arias IM, Boyer JL, Chisari EV, Fausto N, Schachter D, Shafritz DA (eds) The liver: biology and pathobiology, 4th edn. Lippincott Williams and Wilkins, Philadelphia, pp 17–25
Zeisberg M, Yang C, Martino M, Duncan MB, Rieder F, Tanjore H, Kalluri R (2007) Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 282:23337–23347
Zimmermann KW (1923) Der feinere Bau der Blutcapillaren. Z Anat 68:29–109
Zimmerman KW (1928) Ueber das Verhaeltnis der Kupfferschen Sternzellen zum Endothel der Leberkapillaren beim Menschen. Z Mikr Anat Forsch 14: 528–548
Zhan S-S, Jiang JX, Wu J, Halsted C, Friedman SL, Zern MA, Torok NJ (2006) Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo. Hepatology 43:435–443
Zhang JX, Pegoli W Jr, Clemens MG (1994) Endothelin-1 induces direct constriction of hepatic sinusoids. Am J Physiol Gastrointest Liver Physiol 266:G624–G632
Zhao C, Chen W, Yang L, Chen L, Stimpson SA, Diehl AM (2006) PPARγ agonists prevent TGFβ1/Smad3-signaling in human hepatic stellate cells. Biochem Biophys Res Commun 350:385–391
Zheng S, Chen A (2004) Activation of PPARγ is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro. Biochem J 384:149–157
Zheng S, Chen A (2006) Curcumin suppresses the expression of extracellular matrix genes in activated hepatic stellate cells by inhibiting gene expression of connective tissue growth factor. Am J Physiol Gastrointest Liver Physiol 290:G883–G893
Zhou Y, Shimizu I, Lu G, Itonaga M, Okamura Y, Shono M, Honda H, Inoue S, Muramatsu M, Ito S (2001) Hepatic stellate cells contain the functional estrogen receptor β but not the estrogen receptor α in male and female rats. Biochem Biophys Res Commun 286:1059–1065
Zhou X, Jamil A, Nash A, Chan J, Trim N, Iredale JP, Benyon RC (2006) Impaired proteolysis of collagen I inhibits proliferation of hepatic stellate cells. Implications for regulation of liver fibrosis. J Biol Chem 281:39757–39765
Zizola CF, Schwartz GJ, Vogel S (2008) Cellular retinol-binding protein type III is a PPAR target gene and plays a role in lipid metabolism. Am J Physiol Endocrinol Metab 295:E1358–E1368
Acknowledgements
We acknowledge Drs. Kenjiro Wake and late Hajime Mannen (Emeritus professors of Tokyo Medical and Dental University), who introduced Haruki Senoo to basic medical research and encouraged the authors continuously. We are grateful to Drs. Tetsuro Kato and Tetsuo Kato (Emeritus professors of Akita University) for their continuous support and encouragement. The authors also thank Dr. Mitsuru Sato and Mr. Naosuke Kojima (Akita University School of Medicine) for valuable discussions and significant techniques.
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Senoo, H., Mezaki, Y. & Fujiwara, M. The stellate cell system (vitamin A-storing cell system). Anat Sci Int 92, 387–455 (2017). https://doi.org/10.1007/s12565-017-0395-9
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DOI: https://doi.org/10.1007/s12565-017-0395-9