MiR-30c-5p inhibits high glucose-induced EMT and renal fibrogenesis by down-regulation of JAK1 in diabetic nephropathy

B.-H. Gao, H. Wu, X. Wang, L.-L. Ji, C. Chen

Department of Nephrology, the Zhongshan Hospital Affiliated to Dalian University, Zhongshan, Dalian, Liaoning, China. 13304110309@163.com

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• Nephrology

OBJECTIVE:  Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus (DM) and has become the major cause of end-stage renal failure. MicroRNAs (miRs) play key roles in many pathologic processes for initiating and progressing, including DN. Epithelial-mesenchymal transition (EMT) and renal fibrogenesis are important features of DN. However, the role of miR-30c-5p in high glucose (HG)-induced EMT and renal fibrogenesis is not clear. This study was aimed at determining the regulatory network of miR-30c-5p and JAK1 in DN.

PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot assays were performed to detect expressions of miR-30c-5p, JAK1, vimentin, α-SMA, and E-cadherin. The possible binding sites between miR-30c-5p and JAK1 were predicted by TargetScan online database and verified by Luciferase report assay. The secretion of fibronectin (FN) and Collagen IV (Col IV) in the supernatant was detected by Enzyme-linked immunosorbent (ELISA) assay.

RESULTS: MiR-30c-5p was downregulated and JAK1 was upregulated in renal fibrosis tissue and HG stimulated HK2 cells. Transfection of miR-30c-5p inhibited HG-induced EMT and renal fibrogenesis in HK2 cells, which was reversed by miR-30c-5p inhibitor. Moreover, JAK1 was confirmed as a direct target of miR-30c-5 and knockdown of JAK1 markedly inhibited HG-induced renal fibrogenesis and EMT in HK2 cells. Furthermore, overexpression of JAK1 attenuated the inhibitory effect of miR-30c-5p on HG-induced EMT and renal fibrogenesis in HK2 cells.

CONCLUSIONS: MiR-30c-5p evidently inhibited HG-induced EMT and renal fibrogenesis by down-regulation JAK1 in DN, providing a promising therapeutic strategy for the treatment of DN.

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