MiR-130a-5p prevents angiotensin II-induced podocyte apoptosis by modulating M-type phospholipase A2 receptor.

ABSTRACT: Podocyte apoptosis is considered as the important element that promotes the development and progress of membranous nephropathy (MN). Unfortunately, the underlying mechanism of podocytes apoptosis in MN remains elusive. We compared the renal expressions of miR-130a-5p and M-type phospholipase A2 receptor (PLA2R) between MN patients (n = 30) and 30 controls by qRT-PCR and western blot, respectively. The podocyte damage model in vitro was established by angiotensin II (Ang II, 100 nmol/L) exposure for 24 h. Interaction between miR-130a-5p and PLA2R was determined using dual-luciferase reporter gene assay. MN mice were induced by intravenous injection of cBSA. In this study, miR-130a-5p expression was significantly decreased both in the renal biopsy specimens from MN patients and podocyte cell line AB8/13 following stimulation of Ang II. Overexpressed miR-130a-5p in AB8/13 cells significantly attenuated the Ang II induced-apoptosis in vitro. In contrast, down-regulated miR-130a-5p induced podocyte apoptosis. PLA2R was identified as the target of miR-130a-5p in AB8/13 cells. And up-regulated or down-regulated PLA2R could obviously attenuate the effect of miR-130a-5p overexpression or knockdown on the apoptosis of AB8/13 cells. Furthermore, it was also observed that overexpressed miR-130a-5p by miR-130a-5p agomir could obviously alleviate renal injury in MN mice. In conclusion, decreased miR-130a-5p was contributed to the pathological mechanism of MN through increasing PLA2R expression, which induced podocyte apoptosis.

SUBMITTER: Liu D 

PROVIDER: S-EPMC6342077 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature