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Kidney fibrosis induced by various irrigation pressures in mouse models of mild and severe hydronephrosis

  • Urology - Original Paper
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Abstract

Objective

We want to study whether the degree of fibrosis in the mild and severe hydronephrosis is different, and whether the irrigation pressure will affect the fibrosis of the hydronephrosis.

Methods

Animal models of mild and severe hydronephrosis in the left kidney were established: 72 healthy C57BL/6 mice were randomly divided into nine groups (eight in each group). The N group was used as a control group, and 0 mmHg pressure perfusion was given. The M and S groups were used as mild and severe hydronephrosis groups, respectively. The mild and severe hydronephrosis groups were subdivided into eight subgroups, M0–M3 and S0–S3. Among them, groups 0, 1, 2, and 3 were perfused with 0 mmHg, 20 mmHg, 60 mmHg, and 100 mmHg, respectively. We investigated the effects of irrigation pressures on renal fibrosis in mild (group M) and heavy (group S) hydronephrosis by quantitative real-time polymerase chain reaction, Western blot analysis, Masson staining and immunohistochemistry staining in mouse models.

Results

Compared with group N, EMT and ECM deposits were significantly aggravated in both the mild and severe hydronephrosis groups, TGF-β signaling pathway-related molecules significantly changed too. In terms of ECM deposition, S2 and S3 are significantly increased compared to S0.The EMT of M2 and M3 changed significantly compared with M0; the EMT of S1, S2 and S3 changed significantly compared with S0.The molecules related to TGF-β signaling pathway also changed: M0 and S0 changed significantly compared with N; M1, M2 and M3 changed significantly compared with M0; compared with S0, S1, S2 and S3 changed significantly.

Conclusion

Compared with mild hydronephrosis, renal fibrosis in severe hydronephrosis is more severe and its tolerance to perfusion pressure is lower. These changes may be related to the TGF-β signalling pathway.

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References

  1. Youn JH, Kim SS, Yu JH et al (2012) Efficacy and safety of emergency ureteroscopic management of ureteral calculi. Korean J Urol 53:632

    Article  PubMed  PubMed Central  Google Scholar 

  2. Knoll T, Daels F, Desai J et al (2017) Percutaneous nephrolithotomy: technique. World J Urol 35:1361–1368

    Article  PubMed  Google Scholar 

  3. Wang J, Zhou DQ, He M et al (2013) Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model. Exp Ther Med 5:1389–1392

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Landman J, Venkatesh R, Ragab M et al (2002) Comparison of intrarenal pressure and irrigant flow during percutaneous nephroscopy with an indwelling ureteral catheter, ureteral occlusion balloon, and ureteral access sheath. Urology 60:584–587

    Article  PubMed  Google Scholar 

  5. Cao Z, Yu W, Li W et al (2013) Acute kidney injuries induced by various irrigation pressures in rat models of mild and severe hydronephrosis. Urology 82:1453–1459

    Article  PubMed  Google Scholar 

  6. Cao Z, Yu W, Li W et al (2015) Oxidative damage and mitochondrial injuries are induced by various irrigation pressures in rabbit models of mild and severe hydronephrosis. PLoS ONE 10:e127143

    Google Scholar 

  7. Seseke F, Thelen P, Ringert R (2004) Characterization of an animal model of spontaneous congenital unilateral obstructive uropathy by cDNA microarray analysis. Eur Urol 45:374–381

    Article  PubMed  CAS  Google Scholar 

  8. Vielhauer V, Anders HJ, Mack M et al (2001) Obstructive nephropathy in the mouse: progressive fibrosis correlates with tubulointerstitial chemokine expression and accumulation of CC chemokine receptor 2- and 5-positive leukocytes. J Am Soc Nephrol 12:1173–1187

    PubMed  CAS  Google Scholar 

  9. Jha V, Garcia-Garcia G, Iseki K et al (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382:260–272

    Article  PubMed  Google Scholar 

  10. Kaissling B, Lehir M, Kriz W (2013) Renal epithelial injury and fibrosis. Biochim Biophys Acta 1832:931–939

    Article  PubMed  CAS  Google Scholar 

  11. Hongtao C, Youling F, Fang H et al. (2018) Curcumin alleviates ischemia reperfusion-induced late kidney fibrosis through the APPL1/Akt signaling pathway. J Cell Physiol 233:8588–8596

    Article  CAS  Google Scholar 

  12. Meng X, Nikolic-Paterson DJ, Lan HY (2014) Inflammatory processes in renal fibrosis. Nat Rev Nephrol 10:493–503

    Article  PubMed  CAS  Google Scholar 

  13. Singh SP, Tao S, Fields TA et al (2015) Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice. Dis Model Mech 8:931–940

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV (2010) Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med 16:535–543

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Bechtel W, McGoohan S, Zeisberg EM et al (2010) Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat Med 16:544–550

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Rockey DC, Bell PD, Hill JA (2015) Fibrosis-A common pathway to organ injury and failure. N Engl J Med 373:96

    Article  PubMed  CAS  Google Scholar 

  17. Duffield JS (2014) Cellular and molecular mechanisms in kidney fibrosis. J Clin Invest 124:2299–2306

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Li Y, Tan X, Dai C et al (2009) Inhibition of integrin-linked kinase attenuates renal interstitial fibrosis. J Am Soc Nephrol 20:1907–1918

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Humphreys BD, Lin SL, Kobayashi A et al (2010) Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 176:85–97

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Li L, Zepeda-Orozco D, Black R, Lin F (2010) Autophagy is a component of epithelial cell fate in obstructive uropathy. Am J Pathol 176:1767–1778

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Lovisa S, LeBleu VS, Tampe B et al (2015) Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat Med 21:998–1009

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Wang B, Komers R, Carew R et al (2012) Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol 23:252–265

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Zafiriou S, Stanners SR, Saad S et al (2005) Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J Am Soc Nephrol 16:638–645

    Article  PubMed  CAS  Google Scholar 

  24. Malhas AN, Abuknesha RA, Price RG (2002) Interaction of the leucine-rich repeats of polycystin-1 with extracellular matrix proteins: possible role in cell proliferation. J Am Soc Nephrol 13:19–26

    PubMed  CAS  Google Scholar 

  25. Tian L, Fu P, Zhou M et al (2016) Role of urotensin II in advanced glycation end product-induced extracellular matrix synthesis in rat proximal tubular epithelial cells. Int J Mol Med 38:1831–1838

    Article  PubMed  CAS  Google Scholar 

  26. Lagares D, Ghassemi-Kakroodi P, Tremblay C et al (2017) ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis. Nat Med 23:1405–1415

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Duffield JS, Lupher M, Thannickal VJ, Wynn TA (2013) Host responses in tissue repair and fibrosis. Annu Rev Pathol 8:241–276

    Article  PubMed  CAS  Google Scholar 

  28. Boutet A, De Frutos CA, Maxwell PH et al (2006) Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J 25:5603–5613

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. LeBleu VS, Taduri G, O’Connell J et al (2013) Origin and function of myofibroblasts in kidney fibrosis. Nat Med 19:1047–1053

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Grande MT, Sanchez-Laorden B, Lopez-Blau C et al (2015) Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat Med 21:989–997

    Article  PubMed  CAS  Google Scholar 

  31. Louis K, Hertig A (2015) How tubular epithelial cells dictate the rate of renal fibrogenesis? World J Nephrol 4:367–373

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kie JH, Kapturczak MH, Traylor A, Agarwal A, Hill-Kapturczak N (2008) Heme oxygenase-1 deficiency promotes epithelial-mesenchymal transition and renal fibrosis. J Am Soc Nephrol 19:1681–1691

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  33. Munoz-Felix JM, Gonzalez-Nunez M, Martinez-Salgado C, Lopez-Novoa JM (2015) TGF-beta/BMP proteins as therapeutic targets in renal fibrosis. Where have we arrived after 25 years of trials and tribulations? Pharmacol Ther 156:44–58

    Article  PubMed  CAS  Google Scholar 

  34. Hills CE, Squires PE (2011) The role of TGF-beta and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev 22:131–139

    PubMed  CAS  Google Scholar 

  35. Daniel C (2008) Blocking of angiotensin II is more than blocking of transforming growth factor-β. Kidney Int 74:551–553

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No.81870471).

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Authors and Affiliations

  1. Department of Urology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, Hubei, China

    Xiaobing Yao, Fan Cheng, Weiming Yu, Ting Rao, Sheng Zhao, Xiangjun Zhou & Jinzhuo Ning

  2. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China

    Wei Li

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  1. Xiaobing Yao
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  2. Fan Cheng
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  5. Wei Li
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Correspondence to Fan Cheng.

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Yao, X., Cheng, F., Yu, W. et al. Kidney fibrosis induced by various irrigation pressures in mouse models of mild and severe hydronephrosis. Int Urol Nephrol 51, 215–222 (2019). https://doi.org/10.1007/s11255-018-2040-5

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  • DOI: https://doi.org/10.1007/s11255-018-2040-5

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