miR-382 Contributes to Renal Tubulointerstitial Fibrosis by Downregulating HSPD1. Oxid Med Cell Longev 2017;2017:4708516
Date
07/07/2017Pubmed ID
28680529Pubmed Central ID
PMC5478870DOI
10.1155/2017/4708516Scopus ID
2-s2.0-85021686907 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
Redox imbalance plays an important role in the pathogenesis of CKD progression. Previously, we demonstrated that microRNA-382 (miR-382) contributed to TGF-β1-induced loss of epithelial polarity in human kidney epithelial cells, but its role in the development of renal tubulointerstitial fibrosis remains unknown. In this study, we found that with 7 days of unilateral ureteral obstruction (UUO) in mice, the abundance of miR-382 in the obstructed kidney was significantly increased. Meanwhile, the protein expression of heat shock protein 60 (HSPD1), a predicted target of miR-382, was reduced after 7 days of UUO. Expression of 3-nitrotyrosine (3-NT) was upregulated, but expression of thioredoxin (Trx) was downregulated. Anti-miR-382 treatment suppressed the upregulation of miR-382, attenuated renal interstitial fibrosis in the obstructed kidney, and reversed the downregulation of HSPD1/Trx and upregulation of 3-NT after UUO. Furthermore, in vitro study revealed that overexpression of HSPD1 significantly restored Trx expression and reversed TGF-β1-induced loss of E-cadherin, while in vivo study found that direct siRNA-mediated suppression of HSPD1 in the UUO kidney promoted oxidative stress despite miR-382 blockade. Our clinical data showed that upregulation of miR-382/3-NT and downregulation of HSPD1/Trx were also observed in IgA nephropathy patients with renal interstitial fibrosis. These data supported a novel mechanism in which miR-382 targets HSPD1 and contributes to the redox imbalance in the development of renal fibrosis.
Author List
Fang Y, Xie T, Xue N, Kuang Q, Wei Z, Liang M, Ding XMESH terms used to index this publication - Major topics in bold
AnimalsCell Line
Chaperonin 60
Down-Regulation
Fibrosis
Glomerulonephritis, IGA
Humans
Kidney Tubules
Male
Mice
Mice, Inbred ICR
MicroRNAs
Mitochondrial Proteins
Transfection
