Dataset Information

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

ACCESS DATA

Publications

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]

PMID: 31746345

Similar Datasets

Project description:Long noncoding RNA (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets