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MiRNA?342 suppresses renal interstitial fibrosis in diabetic nephropathy by targeting SOX6.


ABSTRACT: Diabetic kidney disease (DKD) is one of the major microvascular complications in patients with type 1 and/or type 2 diabetes, the first cause of end?stage renal disease (ESRD) in several countries and regions. However, the pathogenesis of DKD and the mechanisms through which it leads to ESRD remain unknown. Thus, in this study, we aimed to elucidate some of these mechanisms. The expression of microRNA (miRNA or miR)?342?3p and SRY?box 6 (SOX6) in the renal tissues of mice with DKD and mouse renal mesangial cells (MCs) was determined by RT?qPCR and western blot analysis. The diabetic kidney environment was established using high?glucose medium. SOX6 was verified as a target gene of miR?342?3p by dual?luciferase activity assay. In addition, western blot analysis was employed to determine the changes in the levels of several biomarkers of fibrosis [transforming growth factor (TGF)??1, fibronectin (FN), collagen IV (referred to as C?IV) and phosphatase and tensin homolog (PTEN)]. Compared with THE control mice, the expression of miR?342?3p in the kidney tissues of mice with DKD was downregulated, whereas that of SOX6 was upregulated. The same phenomenon was observed in the MCs cultured in high?glucose medium. Subsequently, miR?342?3p inhibited SOX6 expression, promoted cell proliferation and inhibited the apoptosis of MCs. Moreover, the overexpression of miR?342?3p suppressed high glucose?induced renal interstitial fibrosis. In addition, it was found that miR?342?3p inhibited SOX6 expression by binding to the 3'?UTR of SOX6. On the whole, the findings of this study demonstrate that miR?342?3p suppresses the progression of DKD by inducing the degradation of SOX6. Thus, the miR?342?3p/SOX6 axis may serve as a novel therapeutic target in the treatment of DKD.

SUBMITTER: Jiang ZH 

PROVIDER: S-EPMC6889927 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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miRNA‑342 suppresses renal interstitial fibrosis in diabetic nephropathy by targeting SOX6.

Jiang Zhen-Huan ZH   Tang Yun-Zhao YZ   Song Hong-Na HN   Yang Min M   Li Bin B   Ni Chang-Lin CL  

International journal of molecular medicine 20191031 1


Diabetic kidney disease (DKD) is one of the major microvascular complications in patients with type 1 and/or type 2 diabetes, the first cause of end‑stage renal disease (ESRD) in several countries and regions. However, the pathogenesis of DKD and the mechanisms through which it leads to ESRD remain unknown. Thus, in this study, we aimed to elucidate some of these mechanisms. The expression of microRNA (miRNA or miR)‑342‑3p and SRY‑box 6 (SOX6) in the renal tissues of mice with DKD and mouse rena  ...[more]

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