MicroRNA-146a/NAPDH oxidase4 decreases reactive oxygen species generation and inflammation in a diabetic nephropathy model

Abstract

The present study investigated the role of microRNA (miR)-146a in a diabetic nephropathy (DN) model, and its molecular mechanism. DN mice were given intraperitoneal injections of streptozotocin (55 mg/kg/day) for 5 consecutive days as an in vivo DN model. The HK-2 human kidney cell line were exposed to 45% D-glucose as an in vitro DN model. Firstly, it was demonstrated that miR-146a expression was inhibited and NAPDH oxidase 4 (Nox4) was increased in DN mice. In HK-2 cells, overexpression of miR-146a inhibited Nox4 protein expression and decreased reactive oxygen species (ROS) generation, oxidative stress and inflammation, and suppressed vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression. Nacetylcysteine, a Nox4 inhibitor, was demonstrated to inhibit ROS generation, suppress VCAM-1 and ICAM-1 protein expression, and decrease oxidative stress and infammation in HK-2 cells following overexpression of miR-146a. In conclusion, these results indicated that miR-146a/Nox4 decreases ROS generation and inflammation and prevents DN. Therefore, miR-146a may represent a novel anti-inflammatory and-oxidative modulator of DN.