Abstract
Matrix metalloproteinases play an important role in the pathogenesis of psoriasis. The aim of this paper was to explore the influence of MMP1 silencing with a specific shRNA on migration and proliferation of epidermal keratinocytes exposed to tumor necrosis factor, as well as changes in the expression of genes involved in their terminal differentiation. Changes in gene expression were analyzed by real-time PCR. The cell proliferation was assessed by comparative analysis of the growth curves. The cell migration was explored by scratch assay. To quantify cell migration, the representative areas of cell cultures were photographed in the equal periods of time and compared to each other. The obtained results demonstrated that an exposure of control cell line to tumor necrosis factor caused changes in the expression of several genes similar to ones that were previously observed in lesional psoriatic skin. Particularly, the expression of MMP9, IVL and KRT16 increased whereas the expression of LOR, KRT1 and-10—decreased. In contrast, MMP1-deficient cells treated with tumor necrosis factor exhibited higher levels of LOR, KRT1 and -10, as well as lower levels KRT16 and -17 compared to control cells treated with the same cytokines. Moreover, MMP1-deficient cells exhibited a lower level of CCNА2 and higher level of CCND1. In this respect, knocking MMP1 down resulted in a lower cell proliferation and migration rates of TNF-treated epidermal keratinocytes. In conclusion, this study demonstrated that MMP1 silencing with specific shRNA can be beneficial for psoriasis. We found that knocking MMP1 down has an antiproliferative effect on epidermal keratinocytes and partially normalizes the expression of cyclins CCNA2, and -D1, as well as the genes involved in the terminal differentiation of this kind of cells (LOR, KRT1, -10, -16 and -17).
Similar content being viewed by others
References
Greb, J.E., Goldminz, A.M., Elder, J.T., et al., Psoriasis, Nat. Rev. Dis. Primers., 2016, vol. 2, no. 16082. doi 10.1038/nrdp.2016.82
Michalek, I.M., Loring, B., and John, S.M., A systematic review of worldwide epidemiology of psoriasis, J. Eur. Acad. Dermatol. Venerol., 2017, vol. 31, no. 2, pp. 205–212. doi 10.1111/jdv.13854
Khamaganova, I.V., Almazova, A.A., Lebedeva, G.A., and Ermachenko, A.V., Psoriasis epidemiology issues, Klinicheskaya Dermatol. Venerol., 2015, no. 1, pp. 12–16. doi 10.17116/klinderma2015112-16
Soboleva, A.G., Mezentsev, A., Zolotorenko, A., et al., Three-dimensional skin models of psoriasis, Cells Tissues Organs, 2014, vol. 199, nos. 5–6, pp. 301–310. doi 10.1159/000369925
Cope, A., Le Friec, G., Cardone, J., et al., The Th1 life cycle: molecular control of IFN-γ to IL-10 switching, Trends Immunol., 2011, vol. 32, no. 6, pp. 278–286. doi 10.1016/j.it.2011.03.010
Di Meglio, P., Villanova, F., and Nestle, F.O., Psoriasis, Cold Spring Harb. Perspect. Med., 2014, vol. 4, no. 8. a015354. doi 10.1101/cshperspect.a015354
Wcisło-Dziadecka, D., Zbiciak-Nylec, M., Brzezińska-Wcisło, L., and Mazurek, U., TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis, Postgrad. Med. J., 2016, vol. 92, no. 1085, pp. 172–178. doi 10.1136/postgradmedj-2015-133419
Kimball, A.B., Bensimon, A.G., Guerin, A., et al., Efficacy and safety of adalimumab among patients with moderate to severe psoriasis with co-morbidities: subanalysis of results from a randomized, double-blind, placebo-controlled, phase III trial, Am. J. Clin. Dermatol., 2011, vol. 12, no. 1, pp. 51–62. doi 10.2165/11530640-000000000-00000
Paller, A.S., Siegfried, E.C., Langley, R.G., et al., Etanercept treatment for children and adolescents with plaque psoriasis, N. Engl. J. Med., 2008, vol. 358, no. 3, pp. 241–251. doi 10.1056/NEJMoa066886
Reich, K., Nestle, F.O., Papp, K., et al., EXPRESS study investigators: infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial, Lancet, 2005, vol. 366, no. 9494, pp. 1367–1374. doi 10.1016/S0140-6736(05)67566-6
Menter, A., Gottlieb, A., Feldman, S.R., et al., Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics, J. Am. Acad. Dermatol., 2008, vol. 58, no. 5, pp. 826–850. doi 10.1016/j.jaad.2008.02.039
Cline, A., Hill, D., Lewallen, R., and Feldman, S.R., Current status and future prospects for biologic treatments of psoriasis, Expert Rev. Clin. Immunol., 2016, vol. 12, no. 12, pp. 1273–1287. doi 10.1080/1744666X.2016.1202115
Starodubtseva, N.L., Sobolev, V.V., Soboleva, A.G., et al., Expression of genes for metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-12) associated with psoriasis, Russ. J. Genet., 2011, vol. 47, no. 9, pp. 1117–1123.
Mogulevtseva, J.A. and Mezentsev, A.V., Optimization of lentiviral transduction in the culture of immortalized epidermal keratinocytes, Progress Modern Sci.: Theor. Pract. Aspects, 2017, no. 13, pp. 123–134.
Chomczynski, P. and Mackey, K., Modification of the TRI reagent procedure for isolation of RNA from polysaccharide and proteoglycan-rich sources, BioTechniques, 1995, vol. 19, no. 6, pp. 942–945.
Ranta, V., Orpana, A., Carpén, O., et al., Human vascular endothelial cells produce tumor necrosis factoralpha in response to proinflammatory cytokine stimulation, Crit. Care Med., 1999, vol. 27, no. 10, pp. 2184–2187.
Köck, A., Schwarz, T., Kirnbauer, R., et al., Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light, J. Exp. Med., 1990, vol. 172, no. 6, pp. 1609–1614.
Bashir, M.M., Sharma, M.R., and Werth, V.P., TNF-α production in the skin, Arch. Dermatol. Res., 2009, vol. 301, no. 1, pp. 87–91. doi 10.1007/s00403-008-0893-7
Gatzka, M., Skin under TNF influence: how regulatory T cells work against macrophages in psoriasis, J. Pathol., 2017, vol. 241, no. 1, pp. 3–5. doi 10.1002/path.4820
Arango Duque, G. and Descoteaux, A., Macrophage cytokines: involvement in immunity and infectious diseases, Front. Immunol., 2014, vol. 5, no. 491. doi 10.3389/fimmu.2014.00491
Janes, K.A., Gaudet, S., Albeck, J.G., et al., The response of human epithelial cells to TNF involves an inducible autocrine cascade, Cell, 2006, vol. 124, no. 6, pp. 1225–1239. doi 10.1016/j.cell.2006. 01.041
Osawa, Y., Nagaki, M., Banno, Y., et al., Tumor necrosis factor alpha-induced interleukin-8 production via NF-κB and phosphatidylinositol 3-kinase/Akt pathways inhibits cell apoptosis in human hepatocytes, Infect. Immun., 2002, vol. 70, no. 11, pp. 6294–6301.
Salamone, G., Giordano, M., Trevani, A.S., et al., Promotion of neutrophil apoptosis by TNF-α, J. Immunol., 2001, vol. 166, no. 5, pp. 3476–3483.
Jin, L. and Wang, G., Keratin 17: a critical player in the pathogenesis of psoriasis, Med. Res. Rev., 2014, vol. 34, no. 2, pp. 438–454. doi 10.1002/med.21291
Pagano, M., Pepperkok, R., Verde, F., et al., Cyclin A is required at two points in the human cell cycle, EMBO J., 1992, vol. 11, no. 3, pp. 961–971.
Matsushime, H., Ewen, M.E., Strom, D.K., et al., Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins, Cell, 1992, vol. 71, no. 2, pp. 323–334.
Prasad, C.P, Gupta, S.D., Rath, G., and Ralhan, R., Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression, Oncology, 2007, vol. 73, nos. 1–2, pp. 112–117. doi 10.1159/000120999
Manczinger, M. and Kemény, L., Novel factors in the pathogenesis of psoriasis and potential drug candidates are found with systems biology approach, PLoS One, 2013, vol. 8, no. 11. e80751. doi 10.1371/journal. pone.0080751
Scott, K.A., Arnott, C.H., Robinson, S.C., et al., TNF-α regulates epithelial expression of MMP-9 and integrin αvβ6 during tumour promotion: a role for TNF-α in keratinocyte migration?, Oncogene, 2004, vol. 23, no. 41, pp. 6954–6966. doi 10.1038/sj.onc.1207915
Jiang, X., Teng, M., Guo, X., et al., Switch from αvβ5 to αvβ6 integrin is required for CD9-regulated keratinocyte migration and MMP-9 activation, FEBS Lett., 2014, vol. 588, no. 21, pp. 4044–4052. doi 10.1016/j.febslet.2014.09.027
Ashmarin, I.P., Karazeeva, E.P., Lyapina, L.A., and Samonina, G.E., The simplest proline-containing peptides PG, GP, PGP, and GPGG: regulatory activity and possible sources of biosynthesis, Biochemistry (Moscow), 1998, vol. 63, no. 2, pp. 119–124.
Wells, J.M., Gaggar, A., and Blalock, J.E., MMP generated matrikines, Matrix Biol., 2015, nos. 44–46, pp. 122–129. doi 10.1016/j.matbio.2015.01.016
Boire, A., Covic, L., Agarwal, A., et al., PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells, Cell, 2005, vol. 120, no. 3, pp. 303–313. doi 10.1016/j.cell.2004.12.018
Author information
Authors and Affiliations
Corresponding author
Additional information
Published in Russian in Genetika, 2018, Vol. 54, No. 8, pp. 948–955.
The article was translated by the authors.
Rights and permissions
About this article
Cite this article
Mogulevtseva, J.A., Mezentsev, A.V. & Bruskin, S.A. Impact of Metalloproteinase 1 Deficiency Induced by Specific Small Hairpin RNA on the Physiological Effects of Tumor Necrosis Factor. Russ J Genet 54, 960–966 (2018). https://doi.org/10.1134/S1022795418080094
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795418080094