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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 4708516, 16 pages
Research Article

miR-382 Contributes to Renal Tubulointerstitial Fibrosis by Downregulating HSPD1

1Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China
2Shanghai Institute of Kidney and Dialysis, Shanghai, China
3Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China
4Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
5Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

Correspondence should be addressed to Mingyu Liang; ude.wcm@gnailm and Xiaoqiang Ding; nc.hs.latipsoh-sz@gnaiqoaix.gnid

Received 2 February 2017; Revised 30 March 2017; Accepted 5 April 2017; Published 7 June 2017

Academic Editor: Jaideep Banerjee

Copyright © 2017 Yi Fang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.