在糖尿病大鼠中，miR-195的上调通过靶向线粒体融合蛋白2加速氧化应激诱导的视网膜内皮细胞损伤。
Upregulation of miR-195 accelerates oxidative stress-induced retinal endothelial cell injury by targeting mitofusin 2 in diabetic rats.
作者信息
Zhang Rui, Garrett Qian, Zhou Huimin, Wu Xiaoxi, Mao Yueran, Cui Ximing, Xie Bing, Liu Zanchao, Cui Dongsheng, Jiang Lei, Zhang Qingfu, Xu Shunjiang
机构信息
Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China.
The University of New South Wales, Sydney, NSW 2052, Australia; The University of Notre Dame Australia, NSW 2008, Australia.
出版信息
Mol Cell Endocrinol. 2017 Sep 5;452:33-43. doi: 10.1016/j.mce.2017.05.009. Epub 2017 May 6.
This study was performed to investigate the oxidative stress-induced miRNA changes in relation to pathogenesis of diabetic retinopathy (DR) and to establish a functional link between miRNAs and oxidative stress-induced retinal endothelial cell injury. Our results demonstrated that oxidative stress could induce alterations of miRNA expression profile, including up-regulation of miR-195 in the diabetic retina or cultured HMRECs after exposed to HO or HG (P < 0.05). Oxidative stress also resulted in a significant reduction of MFN2 expression in diabetic retina or HMRECs (P < 0.05). Overexpression of miR-195 reduced MFN2 protein levels, and induced tube formation and increased permeability of diabetic retinal vasculature. The luciferase reporter assay confirmed that miR-195 binds to the 3' -untranslated region (3'-UTR) of MFN2 mRNA. This study suggested that miR-195 played a critical role in oxidative stress-induced retinal endothelial cell injury by targeting MFN2 in diabetic rats.
本研究旨在探讨氧化应激诱导的微小RNA（miRNA）变化与糖尿病视网膜病变（DR）发病机制的关系，并建立miRNA与氧化应激诱导的视网膜内皮细胞损伤之间的功能联系。我们的结果表明，氧化应激可诱导miRNA表达谱的改变，包括糖尿病视网膜或培养的人微血管视网膜内皮细胞（HMRECs）在暴露于过氧化氢（HO）或高糖（HG）后miR-195的上调（P < 0.05）。氧化应激还导致糖尿病视网膜或HMRECs中MFN2表达显著降低（P < 0.05）。miR-195的过表达降低了MFN2蛋白水平，并诱导了糖尿病视网膜血管的管腔形成和通透性增加。荧光素酶报告基因检测证实miR-195与MFN2 mRNA的3'非翻译区（3'-UTR）结合。本研究提示，在糖尿病大鼠中，miR-195通过靶向MFN2在氧化应激诱导的视网膜内皮细胞损伤中起关键作用。
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