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MiR-32-5p knockdown inhibits epithelial to mesenchymal transition and renal fibrosis by targeting SMAD7 in diabetic nephropathy.
Human & Experimental Toxicology ( IF 2.8 ) Pub Date : 2020-09-22 , DOI: 10.1177/0960327120952157
H-J Wang 1 , H Liu 1 , Y-H Lin 1 , S-J Zhang 1
Affiliation  

Diabetic nephropathy (DN) is primary cause of end-stage renal disease. A previous study has shown that miR-32-5p (miR-32) is highly expressed in kidney tissue during chronic allograft dysfunction with interstitial fibrosis and tubular atrophy. However, the role of miR-32-5p (miR-32) in DN is still unclear. In this study, streptozotocin-induced DN rat models and high glucose (HG)-incubated human kidney proximal tubular epithelial (HK-2) cells were established to investigate the role and underlying mechanisms of miR-32 in DN. Results of real-time PCR revealed that miR-32 levels were greatly increased in DN rats and HG-incubated HK-2 cells. Downregulation of miR-32 effectively relieved HG-induced autophagy suppression, fibrosis, epithelial-mesenchymal transition (EMT) and inflammation in HK-2 cells. Besides, miR-32 overexpression significantly down-regulated the expression of mothers against decapentaplegic homolog 7 (SMAD7), whereas knockdown of miR-32 markedly up-regulated the level of SMAD7. Dual-luciferase reporter gene assay confirmed that SMAD7 was a target of miR-32. Reintroduction of SMAD7 expression rescued miR-32-induced HK-2 cells autophagy suppression, EMT and renal fibrosis. Our findings indicate that miR-32 may play roles in the progression of EMT and fibrosis in DN.



中文翻译:

MiR-32-5p 敲低通过靶向糖尿病肾病中的 SMAD7 来抑制上皮间质转化和肾纤维化。

糖尿病肾病 (DN) 是终末期肾病的主要原因。先前的一项研究表明,在伴有间质纤维化和肾小管萎缩的慢性同种异体移植功能障碍期间,miR-32-5p(miR-32)在肾组织中高表达。然而,miR-32-5p (miR-32) 在 DN 中的作用仍不清楚。在这项研究中,建立链脲佐菌素诱导的 DN 大鼠模型和高糖 (HG) 孵育的人肾近端肾小管上皮 (HK-2) 细胞,以研究 miR-32 在 DN 中的作用和潜在机制。实时 PCR 的结果显示 DN 大鼠和 HG 孵育的 HK-2 细胞中的 miR-32 水平大大增加。miR-32 的下调有效地缓解了 HG 诱导的 HK-2 细胞自噬抑制、纤维化、上皮间质转化 (EMT) 和炎症。除了,miR-32 过表达显着下调母亲对十无性瘫痪同源物 7 (SMAD7) 的表达,而敲除 miR-32 则显着上调 SMAD7 的水平。双荧光素酶报告基因检测证实 SMAD7 是 miR-32 的靶标。重新引入 SMAD7 表达挽救了 miR-32 诱导的 HK-2 细胞自噬抑制、EMT 和肾纤维化。我们的研究结果表明 miR-32 可能在 DN 的 EMT 和纤维化进展中发挥作用。

更新日期:2020-09-22
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