Down-regulated miR-187 promotes oxidative stress-induced retinal cell apoptosis through P2X7 receptor
Down-regulated miR-187 promotes oxidative stress-induced retinal cell apoptosis through P2X7 receptor
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下调miR-187通过P2X7受体促进氧化应激诱导的视网膜细胞凋亡
DOI：
10.1016/j.ijbiomac.2018.08.166
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发表时间：
2018
影响因子：
8.2
通讯作者：
Tian-Zi Zhang
中科院分区：
文献类型：
--
作者：
Qiu-Li Zhang;Wei Wang;Alatantuya;Dongmei;Zhan-Jun Lu;Lan-Lan Li;Tian-Zi Zhang
视网膜中表达的多种microRNA（miRNAs）已被证实参与视网膜细胞凋亡，与视网膜疾病的发生发展密切相关。我们前期的研究已经证实了miR-187在视网膜细胞凋亡中的重要作用。本研究旨在进一步阐明miR-187在RGC-5细胞凋亡中的确切作用及其可能机制。通过活性氧（ROS）和丙二醛（MDA）水平评估细胞氧化应激状态。我们的研究结果表明，升高的压力，谷氨酸和H2 O2诱导的RGC-5细胞中的氧化应激伴随着miR-187表达的减少和P2 X7 R表达的增加。然而，miR-187的过表达逆转了RGC-5细胞中氧化应激的这种激活。此外，miR-187可能通过与P2 X7 R的3′UTR相互作用，负调控P2 X7 R，从而抑制氧化应激诱导的RGC-5细胞凋亡。最后，我们证实了miR-187的强制表达减轻了慢性高眼压大鼠模型视网膜组织中的氧化应激损伤。我们的数据表明，miR-187/P2 X7 R信号转导参与视网膜细胞凋亡，至少部分，通过激活氧化应激。
Several microRNAs (miRNAs) expressed in the retina were confirmed to involve in retinal cell apoptosis, which was closely linked with the development of retinal diseases. Our previous studies have confirmed a vital role of miR-187 in retinal cells apoptosis. The aim of this study was to further elucidate the precise role of miR-187 and its probable mechanisms in RGC-5 cells apoptosis. The cellular oxidative stress status was assessed by reactive oxygen species (ROS) production and malondialdehyde (MDA) level. Our results showed that the elevated pressure, glutamate and H2O2-induced oxidative stress in RGC-5 cells was accompanied by a decrease in miR-187 expression and an increase in P2X7R expression. However, overexpression of miR-187 reversed this activation of oxidative stress in RGC-5 cells. Moreover, we also revealed that miR-187 inhibited the oxidative stress-induced apoptosis of RGC-5 cells through negative regulating P2X7R, probably through interacting with the 3′UTR of P2X7R. Finally, we confirmed that the forced miR-187 expression alleviated oxidative stress injury in retina tissues of rat models with chronic ocular hypertension. Our data demonstrated that miR-187/P2X7R signaling was involved in retinal cell apoptosis, at least in part, through activating oxidative stress.