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 inflammation 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.

journal_name

Mol Med Rep

authors

Wan RJ,Li YH

doi

10.3892/mmr.2018.8407

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

4759-4766

issue

3

eissn

1791-2997

issn

1791-3004

journal_volume

17

pub_type

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