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.

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

“…Further analysis is required to explore the effect of miR-125b in renal diseases. miR-130a: Liang et al reported that miR-130a protected LPS-induced glomerular injury by Klotho upregulation [67]. They also indicated that miR-130a activated PI3K/AKT pathway and inhibited Wnt and NF-κB pathway [67].…”

“…miR-130a: Liang et al reported that miR-130a protected LPS-induced glomerular injury by Klotho upregulation [67]. They also indicated that miR-130a activated PI3K/AKT pathway and inhibited Wnt and NF-κB pathway [67]. Liu et al reported that miR-130a-5p prevented angiotensin II-induced podocyte apoptosis by modulating phospholipase A2 receptor (PLA2R) [68].…”

MicroRNAs as Biomarkers for Nephrotic Syndrome

“…Rahbar et al analyzed the expression pattern of the glucocorticoid receptors α and β, and their epigenetic regulators, miR-24, miR-30a and miR-370 in peripheral blood mononuclear cells, and reported that the increase in miR-30a and miR-370 levels as well as the decrease in miR-24 levels were observed in MGN patients compared to FSGS patients, while no significant differences in glucocorticoid receptors α and β expressions were observed between MGN, FSGS and healthy controls, indicating that dysregulation levels of glucocorticoid receptors α and β were not attributed to steroid resistance [ 36 ]. Liu et al found that miR-130-5p potentially regulates PLA2R1 and, thus, investigated the correlation between miR-130-5p and MGN, and reported the decreased expression of miR-130-5p in kidneys of MGN patients [ 37 ]. They conducted animal experiments and demonstrated that the decrease in miR-130a-5p expression may increase PLA2R expression, thereby inducing podocyte apoptosis.…”

Circ_0000524/miR‐500a‐5p/CXCL16 axis promotes podocyte apoptosis in membranous nephropathy

“…A study has reported that miR‐130a‐5p prevents angiotensin II‐induced podocyte apoptosis by modulating M‐type Phospholipase A2 Receptor 21 . Similarly, we established the podocyte injury model by AngII in vitro.…”