Department of Ophthalmology, Affiliated Hospital of Inner Mongolia University for the Nationalities, No. 1742, HuoLinHe Street, Tongliao, Neimenggu 028050, China.
Department of Ophthalmology, Tongliao Hospital, No. 668, KeErQin Street, Tongliao, Neimenggu 028000, China.
Int J Biol Macromol. 2018 Dec;120(Pt A):801-810. doi: 10.1016/j.ijbiomac.2018.08.166. Epub 2018 Aug 28.
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 HO-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.
几种在视网膜中表达的 microRNAs（miRNAs）被证实参与视网膜细胞凋亡，这与视网膜疾病的发生密切相关。我们之前的研究已经证实 miR-187 在视网膜细胞凋亡中起着重要作用。本研究旨在进一步阐明 miR-187 在 RGC-5 细胞凋亡中的精确作用及其可能的机制。通过活性氧（ROS）产生和丙二醛（MDA）水平来评估细胞氧化应激状态。我们的结果表明，升高的压力、谷氨酸和 HO 诱导的 RGC-5 细胞氧化应激伴随着 miR-187 表达的降低和 P2X7R 表达的增加。然而，miR-187 的过表达逆转了 RGC-5 细胞中这种氧化应激的激活。此外，我们还揭示了 miR-187 通过负调控 P2X7R 抑制氧化应激诱导的 RGC-5 细胞凋亡，可能通过与 P2X7R 的 3'UTR 相互作用。最后，我们证实强制表达 miR-187 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/P2X7R 信号通路至少部分通过激活氧化应激参与视网膜细胞凋亡。
