MicroRNA‐26a alleviates tubulointerstitial fibrosis in diabetic kidney disease by targeting PAR4

Abstract

AbstractOur previous study found that miR‐26a alleviates aldosterone‐induced tubulointerstitial fibrosis (TIF). However, the effect of miR‐26a on TIF in diabetic kidney disease (DKD) remains unclear. This study clarifies the role and possible mechanism of exogenous miR‐26a in controlling the progression of TIF in DKD models. Firstly, we showed that miR‐26a was markedly decreased in type 2 diabetic db/db mice and mouse tubular epithelial cells (mTECs) treated with high glucose (HG, 30 mM) using RT‐qPCR. We then used adeno‐associated virus carrying miR‐26a and adenovirus miR‐26a to enhance the expression of miR‐26a in vivo and in vitro. Overexpressing miR‐26a alleviated the TIF in db/db mice and the extracellular matrix (ECM) deposition in HG‐stimulated mTECs. These protective effects were caused by reducing expression of protease‐activated receptor 4 (PAR4), which involved in multiple pro‐fibrotic pathways. The rescue of PAR4 expression reversed the anti‐fibrosis activity of miR‐26a. We conclude that miR‐26a alleviates TIF in DKD models by directly targeting PAR4, which may provide a novel molecular strategy for DKD therapy.