Down-regulation of miR-186 contributes to podocytes apoptosis in membranous nephropathy

作者：Sha, Wen-gang; Shen, Lei; Zhou, Ling; Xu, De-yu; Lu, Guo-yuan^*

来源：Biomedicine & Pharmacotherapy, 2015, 75: 179-184.

DOI：10.1016/j.biopha.2015.07.021

• Membranous nephropathy
• miR-186
• Podocyte
• Toll like receptor
• P2 x 7

Background and aim: Podocytes apoptosis is the key process in the development of membranous nephropathy and miR-186 is reported to be related with cell apoptosis. Here we investigated the expression of miR-186 in membranous nephropathy (MGN) patients and the mechanism underlying the podocytes apoptosis. @@@ Methods: Thirty patients with MGN and 30 healthy people were included in this study. The expression of miR-186 was detected in renal tissue and podocyte cells exposed to AngII by real-time PCR. Caspase-3 activity was used to evaluate podocytes apoptosis. TLR4 and P2 x 7 protein expression was quantified by western blotting. miR-186 inhibitor and miR-186 mimic were transfected into cells to investigate the mechanism underlying miR-186 in podocytes apoptosis. @@@ Results: In MGN patients, the level of miR-186 was significantly down-regulated as well as the protein expression of TLR4 and P2 x 7 was up-regulated in renal tissue. In vitro experiments, TLR4 siRNA increased the expression of miR-186 and miR-186 inhibitor elevated the mRNA and protein expression of P2 x 7 in podocytes exposed to AngII. In addition, the level of cleaved-caspase-3 was up-regulated by miR-186 inhibitor. The TUNEL-positive cells and caspase-3 activity of podocytes induced by AngII were down-regulated by miR-186 mimic. @@@ Conclusions: We revealed that TLR4 is involved in the regulation of miR-186 expression, and the antiapoptotic effect of miR-186 on podocytes is correlated with P2 x 7 regulation.

• 出版日期2015-10
• 单位苏州大学