MiR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy via inhibiting SIRT1 signaling pathway

Protection against renal fibrosis is important for the management of obstructive nephropathy. We researched the roles and possible mechanism of miR-155-5p in renal interstitial fibrosis, which may provide a potential endogenous target for renal interstitial fibrosis in obstructive nephropathy. Herein, NRK-49F cells were transfected with miR-155-5p mimic, miR-155-5p inhibitor, SIRT1 plasmid and/or SIRT1 siRNA. The unilateral ureteral obstruction (UUO) model was built with male C57 black mice and administrated with SRT1720 by tail vein injection. Levels of miR-155-5p, SIRT1 and relative proteins (TGF-beta 1, alpha-SMA, Collage I and fibronectin) in NRK-49F cells or mice kidney tissues were measured with quantitative reverse transcription polymerase chain reaction or Western blot. The target gene of miR-155-5p was analyzed through TargetScan and dual-luciferase reporter assay. Mice kidney tissue was stained with Masson trichrome. It was found that miR-155-5p overexpression promoted the expressions of fibroblast related proteins expression and inhibited the SIRT1 expression in NRK-49F cells, while miR-155-5p silencing had an opposite effect. SIRT1 can bind with miR-155-5p. MiR-155-5p inhibited the level of SIRT1. Fibroblast related proteins were up-regulated by miR-155-5p and down-regulated by SIRT1 in NRK-49F cells, while the up-regulatory effect of miR-155-5p was reversed by SIRT1. MiR-155-5p expression was up-regulated and SIRT1 expression was down-regulated in the kidney tissue of UUO mice. SRT1720 attenuated the fiber deposition, up-regulated SIRT1 level and down-regulated the levels of fibroblast related proteins in UUO model mice. To conclude, miR-155-5p promotes renal interstitial fibrosis in obstructive nephropathyviainhibiting SIRT1 signaling pathway.

Automated summary

The research showed that miR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy by inhibiting the SIRT1 signaling pathway. Additionally, SRT1720 could attenuate fiber deposition, increase SIRT1 levels, and decrease levels of fibroblast-related proteins in UUO model mice.