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miR-124-3p 通过抑制 STAT3 通路抑制视网膜神经胶质细胞功能障碍减轻氧诱导的视网膜病变小鼠的视网膜新生血管形成。

MicroRNA-124-3p Attenuated Retinal Neovascularization in Oxygen-Induced Retinopathy Mice by Inhibiting the Dysfunction of Retinal Neuroglial Cells through STAT3 Pathway.

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.

出版信息

Int J Mol Sci. 2023 Jul 21;24(14):11767. doi: 10.3390/ijms241411767.

Abstract

MicroRNA (miRNA) is a non-coding RNA that can regulate the expression of many target genes, and it is widely involved in various important physiological activities. MiR-124-3p was found to associate with the normal development of retinal vessels in our previous study, but the mechanism of its anti-angiogenic effect on pathological retinal neovascularization still needed to be explored. Therefore, this study aimed to investigate the effect and mechanism of miR-124-3p on retinal neovascularization in mice with oxygen-induced retinopathy (OIR). Here, we found that intravitreal injection of miR-124-3p agomir attenuated pathological retinal neovascularization in OIR mice. Moreover, miR-124-3p preserved the astrocytic template, inhibited reactive gliosis, and reduced the inflammatory response as well as necroptosis. Furthermore, miR-124-3p inhibited the signal transducer and activator of transcription 3 (STAT3) pathway and decreased the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. Taken together, our results revealed that miR-124-3p inhibited retinal neovascularization and neuroglial dysfunction by targeting STAT3 in OIR mice.

摘要

MicroRNA (miRNA) 是一种非编码 RNA,可以调节许多靶基因的表达,广泛参与各种重要的生理活动。我们之前的研究发现 miR-124-3p 与视网膜血管的正常发育有关,但它对病理性视网膜新生血管形成的抗血管生成作用的机制仍需要探索。因此,本研究旨在探讨 miR-124-3p 对氧诱导视网膜病变(OIR)小鼠视网膜新生血管的作用及其机制。在这里,我们发现眼内注射 miR-124-3p 激动剂可减轻 OIR 小鼠的病理性视网膜新生血管形成。此外,miR-124-3p 可保持星形胶质细胞模板,抑制反应性神经胶质增生,并减少炎症反应和坏死性凋亡。此外,miR-124-3p 抑制信号转导和转录激活因子 3(STAT3)通路,降低缺氧诱导因子-1α 和血管内皮生长因子的表达。综上所述,我们的研究结果表明,miR-124-3p 通过靶向 STAT3 抑制 OIR 小鼠的视网膜新生血管形成和神经胶质功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d80d/10380620/c0e8f8af6f1e/ijms-24-11767-g002.jpg

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