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 Repjournal_title
Molecular medicine reportsauthors
Wan RJ,Li YHdoi
10.3892/mmr.2018.8407subject
Has Abstractpub_date
2018-03-01 00:00:00pages
4759-4766issue
3eissn
1791-2997issn
1791-3004journal_volume
17pub_type
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