Down-regulation of miR-23a inhibits high glucose-induced EMT and renal fibrogenesis by up-regulation of SnoN

Springer Science and Business Media LLC - Tập 31 - Trang 22-32 - 2017
Haiping Xu1, Fuyun Sun1, Xiuli Li1, Lina Sun1
1Urology Department, Cangzhou Central Hospital, Hebei, People’s Republic of China

Tóm tắt

It has been reported that transforming growth factor-β1 (TGF-β1) signaling plays an important role in the development of diabetic nephropathy (DN). The nuclear transcription co-repressor Ski-related novel protein N (SnoN) is a critical negative regulator of TGF-β1/Smad signal pathway, involving in tubule epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and tubulointerstitial fibrosis. In this study, we focused on miR-23a as a regulator of SnoN. Our purpose is to study the effects of miR-23a on high glucose (HG)-induced EMT process and ECM deposition in HK2 cells. We found that miR-23a was up-regulated in renal tissues of diabetic patients and HG-induced HK2 cells. Besides, the high level of miR-23a was closely associated with decreased SnoN expression. Knockdown of miR-23a increased SnoN expression and in turn suppressed HG-induced EMT and renal fibrogenesis. Introduction of miR-23a decreased SnoN expression and enhanced the profibrogenic effects of HG on HK2 cells. Next, bioinformatics analysis predicted that the SnoN was a potential target gene of miR-23a. Luciferase reporter assay demonstrated that miR-23a could directly target SnoN. We demonstrated that overexpression of SnoN was sufficient to inhibit HG-induced EMT and renal fibrogenesis in HK2 cells. Furthermore, down-regulation of SnoN partially reversed the protective effect of miR-23a knockdown on HG-induced EMT and renal fibrogenesis in HK2 cells. Collectively, miR-23a and SnoN significantly impact on the progression of HG-induced EMT and renal fibrogenesis in vitro, and they may represent novel targets for the prevention strategies of renal fibrosis in the context of DN.

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Springer Science and Business Media LLC

Tập 31

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