Department of Urology, Hospital of Tianjin Nankai, Nankai, Tianjin 300100, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4759-4766. doi: 10.3892/mmr.2018.8407. Epub 2018 Jan 9.
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.
本研究探讨了 microRNA（miR）-146a 在糖尿病肾病（DN）模型中的作用及其分子机制。DN 小鼠连续 5 天腹腔注射链脲佐菌素（55mg/kg/天）作为体内 DN 模型。将 HK-2 人肾细胞系暴露于 45% D-葡萄糖中作为体外 DN 模型。首先，研究表明 miR-146a 的表达受到抑制，DN 小鼠中 NAPDH 氧化酶 4（Nox4）增加。在 HK-2 细胞中，miR-146a 的过表达抑制 Nox4 蛋白表达，减少活性氧（ROS）生成、氧化应激和炎症，并抑制血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）蛋白表达。N-乙酰半胱氨酸（Nox4 抑制剂）被证明可抑制 ROS 生成，抑制 HK-2 细胞中转录后 miR-146a 过表达后 VCAM-1 和 ICAM-1 蛋白表达，降低氧化应激和炎症。综上所述，这些结果表明 miR-146a/Nox4 可减少 ROS 生成和炎症，预防 DN。因此，miR-146a 可能是一种新型的 DN 抗炎和抗氧化调节剂。
