Repression of microRNA‐382 inhibits glomerular mesangial cell proliferation and extracellular matrix accumulation via FoxO1 in mice with diabetic nephropathy

Abstract

Objectives

Diabetic nephropathy ( DN) is a nerve damaging disorder, characterized by glomerular mesangial cell expansion and accumulation of extracellular matrix ( ECM) proteins. In this study, we aimed to investigate mesangial cell proliferation and ECM accumulation when promoting or suppressing endogenous miR‐382 in glomerular mesangial cells of DN.

Materials and methods

Model establishment consisted of DN induction by streptozotocin ( STZ) in mice. The underlying regulatory mechanisms of miR‐382 were analysed in concert with the treatment of miR‐382 mimics, miR‐382 inhibitors or si RNA against FoxO1 in cultured glomerular mesangial cells isolated from DN mice.

Results

FoxO1 was identified as the downregulated gene in DN based on the microarray data of GSE1009. We found that miR‐382 was significantly upregulated in renal tissues of DN mice and its downregulation dephosphorylated FoxO1, reduced glomerular mesangial cell proliferation and ECM accumulation in vitro. The determination of luciferase activity suggested that miR‐382 negatively targeted FoxO1. Expectedly, distinct levels of phosphorylated FoxO1 were observed in the renal cortices of DN mice, while the silencing of FoxO1 was found to increase glomerular mesangial cell proliferation and ECM accumulation in vitro. Reduced glomerular mesangial cell proliferation and ECM accumulation elicited by miR‐382 inhibitors were reversed by silencing FoxO1.

Conclusions

This study demonstrates miR‐382 suppression exerts a potent anti‐proliferative effect that may be applied to inhibit glomerular mesangial cell proliferation and ECM accumulation in DN.