微小 RNA-145 通过调控 TLR4/NF-κB 信号通路减轻高糖诱导的视网膜内皮细胞氧化应激和炎症反应。

MicroRNA-145 attenuates high glucose-induced oxidative stress and inflammation in retinal endothelial cells through regulating TLR4/NF-κB signaling.

机构信息

Department of Ophthalmology, No.1 People's Hospital of Jining City, Jining, Shandong, China.

出版信息

Life Sci. 2018 Aug 15;207:212-218. doi: 10.1016/j.lfs.2018.06.005. Epub 2018 Jun 5.

DOI:10.1016/j.lfs.2018.06.005

Abstract

Diabetic retinopathy (DR) remains a leading cause of blindness in adults with diabetes mellitus. The pathogenesis of DR is a multifactorial process, and excessive oxidative stress and apoptosis in retinal endothelial cells (RECs) play vital roles. In this study, RECs were treated with 25 mM glucose for three days, and we found that miR-145 was significantly downregulated in high glucose (HG)-treated RECs. Overexpression of miR-145 attenuated the HG-induced apoptosis, oxidative stress and inflammatory cytokines secretion in RECs. Besides, miR-145 overexpression also attenuated the increased TLR4 expression and NF-κB p65 nuclear translocation in HG-treated RECs. Luciferase reporter assay showed that miR-145 could specifically bind to the 3'UTR of TLR4, and overexpression of TLR4 abrogated the beneficial effects of miR-145 in HG-treated RECs. Therefore we suggested that miR-145 might be a potential therapeutic target for DR.

摘要

糖尿病性视网膜病变（DR）仍然是糖尿病成年患者致盲的主要原因。DR 的发病机制是一个多因素的过程，视网膜内皮细胞（RECs）中过量的氧化应激和细胞凋亡起着至关重要的作用。在这项研究中，我们用 25mM 葡萄糖处理 RECs 三天，发现 miR-145 在高糖（HG）处理的 RECs 中显著下调。miR-145 的过表达减轻了 HG 诱导的 RECs 凋亡、氧化应激和炎性细胞因子的分泌。此外，miR-145 的过表达还减轻了 HG 处理的 RECs 中 TLR4 表达的增加和 NF-κB p65 核易位。荧光素酶报告基因检测表明，miR-145 可以特异性结合 TLR4 的 3'UTR，而过表达 TLR4 则消除了 miR-145 在 HG 处理的 RECs 中的有益作用。因此，我们认为 miR-145 可能是 DR 的一个潜在治疗靶点。