Skip to main content
Top
Published in: International Urology and Nephrology 2/2019

01-02-2019 | Urology - Original Paper

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

Authors: Xiaobing Yao, Fan Cheng, Weiming Yu, Ting Rao, Wei Li, Sheng Zhao, Xiangjun Zhou, Jinzhuo Ning

Published in: International Urology and Nephrology | Issue 2/2019

Login to get access

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.
Literature
2.
go back to reference Knoll T, Daels F, Desai J et al (2017) Percutaneous nephrolithotomy: technique. World J Urol 35:1361–1368CrossRefPubMed Knoll T, Daels F, Desai J et al (2017) Percutaneous nephrolithotomy: technique. World J Urol 35:1361–1368CrossRefPubMed
3.
go back to reference 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 5:1389–1392CrossRefPubMedPubMedCentral 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 5:1389–1392CrossRefPubMedPubMedCentral
4.
go back to reference 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 60:584–587CrossRefPubMed 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 60:584–587CrossRefPubMed
5.
go back to reference 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 82:1453–1459CrossRefPubMed 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 82:1453–1459CrossRefPubMed
6.
go back to reference 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 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
7.
go back to reference Seseke F, Thelen P, Ringert R (2004) Characterization of an animal model of spontaneous congenital unilateral obstructive uropathy by cDNA microarray analysis. Eur Urol 45:374–381CrossRefPubMed Seseke F, Thelen P, Ringert R (2004) Characterization of an animal model of spontaneous congenital unilateral obstructive uropathy by cDNA microarray analysis. Eur Urol 45:374–381CrossRefPubMed
8.
go back to reference 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 12:1173–1187PubMed 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 12:1173–1187PubMed
9.
go back to reference Jha V, Garcia-Garcia G, Iseki K et al (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382:260–272CrossRefPubMed Jha V, Garcia-Garcia G, Iseki K et al (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382:260–272CrossRefPubMed
10.
go back to reference Kaissling B, Lehir M, Kriz W (2013) Renal epithelial injury and fibrosis. Biochim Biophys Acta 1832:931–939CrossRefPubMed Kaissling B, Lehir M, Kriz W (2013) Renal epithelial injury and fibrosis. Biochim Biophys Acta 1832:931–939CrossRefPubMed
11.
go back to reference 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 233:8588–8596CrossRef 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 233:8588–8596CrossRef
12.
go back to reference Meng X, Nikolic-Paterson DJ, Lan HY (2014) Inflammatory processes in renal fibrosis. Nat Rev Nephrol 10:493–503CrossRefPubMed Meng X, Nikolic-Paterson DJ, Lan HY (2014) Inflammatory processes in renal fibrosis. Nat Rev Nephrol 10:493–503CrossRefPubMed
13.
go back to reference 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 8:931–940CrossRefPubMedPubMedCentral 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 8:931–940CrossRefPubMedPubMedCentral
14.
go back to reference 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 16:535–543CrossRefPubMedPubMedCentral 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 16:535–543CrossRefPubMedPubMedCentral
15.
16.
go back to reference Rockey DC, Bell PD, Hill JA (2015) Fibrosis-A common pathway to organ injury and failure. N Engl J Med 373:96CrossRefPubMed Rockey DC, Bell PD, Hill JA (2015) Fibrosis-A common pathway to organ injury and failure. N Engl J Med 373:96CrossRefPubMed
18.
19.
go back to reference 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 176:85–97CrossRefPubMedPubMedCentral 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 176:85–97CrossRefPubMedPubMedCentral
20.
21.
go back to reference 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 21:998–1009CrossRefPubMedPubMedCentral 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 21:998–1009CrossRefPubMedPubMedCentral
22.
go back to reference 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 23:252–265CrossRefPubMedPubMedCentral 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 23:252–265CrossRefPubMedPubMedCentral
23.
go back to reference 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 16:638–645CrossRefPubMed 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 16:638–645CrossRefPubMed
24.
go back to reference 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 13:19–26PubMed 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 13:19–26PubMed
25.
go back to reference 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 38:1831–1838CrossRefPubMed 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 38:1831–1838CrossRefPubMed
26.
go back to reference Lagares D, Ghassemi-Kakroodi P, Tremblay C et al (2017) ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis. Nat Med 23:1405–1415CrossRefPubMedPubMedCentral Lagares D, Ghassemi-Kakroodi P, Tremblay C et al (2017) ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis. Nat Med 23:1405–1415CrossRefPubMedPubMedCentral
27.
go back to reference Duffield JS, Lupher M, Thannickal VJ, Wynn TA (2013) Host responses in tissue repair and fibrosis. Annu Rev Pathol 8:241–276CrossRefPubMed Duffield JS, Lupher M, Thannickal VJ, Wynn TA (2013) Host responses in tissue repair and fibrosis. Annu Rev Pathol 8:241–276CrossRefPubMed
28.
go back to reference Boutet A, De Frutos CA, Maxwell PH et al (2006) Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J 25:5603–5613CrossRefPubMedPubMedCentral Boutet A, De Frutos CA, Maxwell PH et al (2006) Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J 25:5603–5613CrossRefPubMedPubMedCentral
30.
go back to reference 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 21:989–997CrossRefPubMed 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 21:989–997CrossRefPubMed
32.
go back to reference 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 19:1681–1691CrossRefPubMedPubMedCentral 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 19:1681–1691CrossRefPubMedPubMedCentral
33.
go back to reference 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 156:44–58CrossRefPubMed 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 156:44–58CrossRefPubMed
34.
go back to reference Hills CE, Squires PE (2011) The role of TGF-beta and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev 22:131–139PubMed Hills CE, Squires PE (2011) The role of TGF-beta and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev 22:131–139PubMed
35.
go back to reference Daniel C (2008) Blocking of angiotensin II is more than blocking of transforming growth factor-β. Kidney Int 74:551–553CrossRefPubMed Daniel C (2008) Blocking of angiotensin II is more than blocking of transforming growth factor-β. Kidney Int 74:551–553CrossRefPubMed
Metadata
Title
Kidney fibrosis induced by various irrigation pressures in mouse models of mild and severe hydronephrosis
Authors
Xiaobing Yao
Fan Cheng
Weiming Yu
Ting Rao
Wei Li
Sheng Zhao
Xiangjun Zhou
Jinzhuo Ning
Publication date
01-02-2019
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 2/2019
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-018-2040-5

Other articles of this Issue 2/2019

International Urology and Nephrology 2/2019 Go to the issue