Effect of miR-29c on renal fibrosis in diabetic rats via the AMPK/mTOR signaling pathway.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES(2019)
摘要
OBJECTIVE: To explore the effect of micro-ribonucleic acid (miR)-29c on renal fibrosis in diabetic rats through the adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway, and to investigate its related mechanism by the research on the effect of miR-29c on the expression of fibrosis-related genes. MATERIALS AND METHODS: The rat model of diabetic nephropathy (DN) was established, and the levels of fasting blood glucose (FBG), 24 h urine protein (24h-Pro), blood urea nitrogen (BUN), and serum creatinine (sCr) were monitored. After the rats were executed, kidney tissues were dissected, stained with paraffin and embedded in hematoxylin and eosin (H&E). Then, Western blotting was used to detect the levels of miR-29c, phosphorylated-AMPK (p-AMPK), alpha-smooth muscle actin (alpha-SMA), tumor necrosis factor-alpha (TNF-alpha), and macrophage migration inhibitory factor (MIF). The human renal tubular epithelial HK-2 cell line was treated with high glucose (HG) to simulate DN cell status in vivo. After that, the expressions of miR-29c and the renal fibrosis marker a-SMA were examined via Western blotting. Finally, the level of alpha-SMA was measured by Western blotting after HG treatment combined with miR-29c silencing. RESULTS: The levels of FBG, BUN, sCr, and 24h-Pro in DN model rats were significantly higher than those in rats of control group. The data manifested that the DN model was successfully established. The expression level of miR-29c in DN model rats was markedly increased and that of the downstream protein p-AMPK also exhibited a significantly increasing trend. In addition, the levels of alpha-SMA, TNF-alpha, and MIF were elevated. The expression levels of miR-29c and a-SMA were increased markedly after the human renal tubular epithelial HK-2 cell line was treated with HG, but the expression of a-SMA was reduced after HG treatment combined with miR-29c silencing for 24 h. CONCLUSIONS: MiR-29c is probably related to the occurrence and development of DN. Besides, miR-29c silencing may inhibit the DN renal fibrosis through AMPK/mTOR signals, so miR-29c may be an effective target for the treatment of DN renal fibrosis.
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关键词
AMPK/mTOR,MiR-29c,Diabetes
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