Key Renal Laboratory of Shenzhen, Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, China.
Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China.
IUBMB Life. 2020 Jul;72(7):1340-1348. doi: 10.1002/iub.2255. Epub 2020 Feb 17.
The aim of the present study was to investigate the molecular mechanism of miR-182 in kidney fibrosis in polycystic kidney disease (PKD). We measured the expression of miR-182 in kidney tissue of autosomal dominant PKD. Additionally, we investigated the relationship between miR-182 and fibrotic protein by transfecting miR-182 mimics and miR-182 inhibitor into polycystic kidney cyst-lined epithelial cells, respectively. Furthermore, we observed the interaction between transforming growth factor β1 (TGF-β1) and miR-182 and fibrinogen factors of cyst-lined epithelial cells after TGF-β1 intervention, and measured the expression of Smad2 and Smad3 protein. Results are presented as follows: (a) MiR-182 was positively correlated with fibrosis of cyst-lined epithelial cells; (b) TGF-β1 could induce fibrosis of cyst-lined epithelial cells; (c) the expression of miR-182 had a remarkably impact on the fibrosis induced by TGF-β1, but had little effect on the expression of TGF-β1; (d) the expression of Smad3 protein in TGF-β1 induce-cyst-lined epithelial cells was increased. TGF-β1 and miR-182 promoting the fibrosis of polycystic kidney cyst-lined epithelial cells may be mediated by the TGF-β1/Smad3 signaling pathway, of which Smad3 was an important regulator.
本研究旨在探讨 miR-182 在多囊肾病(PKD)肾纤维化中的分子机制。我们测量了常染色体显性多囊肾病患者肾组织中 miR-182 的表达。此外,我们通过转染 miR-182 模拟物和 miR-182 抑制剂分别研究了 miR-182 与纤维蛋白原蛋白之间的关系。进一步观察 TGF-β1 干预后 TGF-β1 与 miR-182 及囊衬上皮细胞纤维原因子的相互作用,并测定 Smad2 和 Smad3 蛋白的表达。结果如下:(a)miR-182 与囊衬上皮细胞纤维化呈正相关;(b)TGF-β1 可诱导囊衬上皮细胞纤维化;(c)miR-182 的表达对 TGF-β1 诱导的纤维化有显著影响,但对 TGF-β1 的表达影响不大;(d)TGF-β1 诱导的囊衬上皮细胞中 Smad3 蛋白的表达增加。TGF-β1 和 miR-182 促进多囊肾病囊衬上皮细胞纤维化可能是通过 TGF-β1/Smad3 信号通路介导的,其中 Smad3 是一个重要的调节因子。