MP58-18 EXOGENOUS HYDROGEN SULFIDE TREATMENT REDUCES RENAL FIBROSIS ASSOCIATED WITH CHRONIC URETERAL OBSTRUCTION BY ATTENUATING EPITHELIAL-MESENCHYMAL TRANSITION

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2016MP58-18 EXOGENOUS HYDROGEN SULFIDE TREATMENT REDUCES RENAL FIBROSIS ASSOCIATED WITH CHRONIC URETERAL OBSTRUCTION BY ATTENUATING EPITHELIAL-MESENCHYMAL TRANSITION Shouzhe Lin, Fazil Visram, Ian Lobb, Weihua Liu, Aaron Haig, Jifu Jiang, Amy Mok, Dameng Lian, Mark E. Wood, Matthew Whiteman, and Alp Sener Shouzhe LinShouzhe Lin More articles by this author , Fazil VisramFazil Visram More articles by this author , Ian LobbIan Lobb More articles by this author , Weihua LiuWeihua Liu More articles by this author , Aaron HaigAaron Haig More articles by this author , Jifu JiangJifu Jiang More articles by this author , Amy MokAmy Mok More articles by this author , Dameng LianDameng Lian More articles by this author , Mark E. WoodMark E. Wood More articles by this author , Matthew WhitemanMatthew Whiteman More articles by this author , and Alp SenerAlp Sener More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.816AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prolonged ureteral obstruction can cause fibrosis, leading to irreversible renal injury and chronic kidney disease. Recent studies suggest that transforming growth factor beta 1 (TGF-β1), a cytokine released by infiltrating inflammatory cells, can initiate epithelial-mesenchymal transition (EMT), thereby causing fibrosis. Currently, there are few preemptive measures available for mitigating renal fibrosis during obstruction. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that mediates physiological processes and can mitigate tissue injury via anti-oxidant and anti-inflammatory properties. The current study investigates the effects of H2S on renal fibrosis and EMT progression in chronic obstructive uropathy. METHODS Male Lewis rats underwent unilateral ureteral obstruction (UUO) via ligation of left ureter. Following UUO, male Lewis rats were given daily injections of either phosphate buffered saline (PBS) or 200 μM/kg GYY 4137 (slow-releasing H2S donor)+PBS for 30 days. Kidneys were removed on day 30 and stained with Masson′s trichrome for histological analysis of renal fibrosis. qRT-PCR and Western blot analysis were completed on renal tissue to assess expression of EMT markers. EMT progression was also analyzed via an in vitro scratch wound assay, whereby a scratch wound was created with a 200μL pipette in a confluent monolayer of pig kidney epithelial cells (LLC-PK1). Cells were serum-starved for 24 hours. Cells were then treated with 10ng/mL TGF-β1 to induce EMT, as well as various doses of GYY 4137. Scratch wound was imaged every half hour for 72 hours. EMT progression was determined as a function of wound closure. RESULTS Histological analysis showed significantly reduced fibrosis (P<0.01) in H2S-treated rats following chronic obstruction when compared to PBS treatment. H2S-treated rats also demonstrated significantly decreased (P<0.05) expression of EMT markers following chronic UUO. TGF-β1-induced progression of EMT in renal epithelial cells was significantly reduced (P<0.05) upon H2S treatment. CONCLUSIONS Our findings suggest that supplemental H2S can mitigate renal fibrosis associated with chronic ureteral obstruction. H2S may represent a preemptive therapy against renal damage associated with obstructive uropathy, potentially improving long-term renal function following resolution of renal obstruction. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e783 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Shouzhe Lin More articles by this author Fazil Visram More articles by this author Ian Lobb More articles by this author Weihua Liu More articles by this author Aaron Haig More articles by this author Jifu Jiang More articles by this author Amy Mok More articles by this author Dameng Lian More articles by this author Mark E. Wood More articles by this author Matthew Whiteman More articles by this author Alp Sener More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...