Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
J Cell Physiol. 2019 Jun;234(6):8873-8887. doi: 10.1002/jcp.27549. Epub 2018 Dec 4.
Retinal neovascularization occurs in various ocular disorders including proliferative diabetic retinopathy and secondary neovascular glaucoma, resulting in blindness. This paper aims to investigate the effect of microRNA-141-3p (miR-141-3p) on retinal neovascularization and retinal ganglion cells (RGCs) in glaucoma mice through the Docking protein 5 (DOK5)-mediated mitogen-activated protein kinase (MAPK) signaling pathway. Chip retrieval and difference analysis were used for the potential mechanism of miR-141-3p on glaucoma. All modeled mice were transfected with different expression of mimic or inhibitor. The expressions of miR-141-3p, DOK5, and related genes and proteins of the MAPK signaling pathway were detected by Reverse transcription quantitative polymerase chain reaction and western blot analysis. Cell proliferation, lumen formation, and apoptosis in the retinal vascular epithelial cells and RGCs were detected using Matrigel angiogenesis and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling assays. Moreover, a total of 63 and 294 differentially expressed genes were obtained in GSE2378 and GSE9944 chips, and 4 genes were within the intersection of the chips. In addition, the results showed that miR-141-3p was found to inhibit the DOK5 gene and activate the MAPK pathway. The number of RGCs, the expression of p38, extracellular-signal-regulated kinases (ERK), Jun N-terminal kinase (JNK), IGF-1, VEGF, HIF1-α, Bax, caspase-3, and the extent of p38, ERK, and JNK phosphorylated were decreased with miR-141-3p upregulation. Lastly, the results obtained showed that miR-141-3p inhibited the proliferation of retinal vascular epithelial cells and inhibited angiogenesis, as well as promoted apoptosis of RGCs. The study suggests that miR-141-3p inhibits retinal neovascularization in glaucoma mice by impeding the activation of the DOK5-mediated MAPK signaling pathway.
视网膜新生血管发生于多种眼部疾病，包括增生性糖尿病视网膜病变和新生血管性青光眼，导致失明。本文旨在通过 Docking 蛋白 5 (DOK5)-介导的丝裂原活化蛋白激酶 (MAPK) 信号通路研究 microRNA-141-3p (miR-141-3p) 对青光眼小鼠视网膜新生血管和视网膜神经节细胞 (RGC) 的影响。芯片检索和差异分析用于探讨 miR-141-3p 对青光眼的潜在机制。所有建模小鼠均转染不同表达的模拟物或抑制剂。采用逆转录定量聚合酶链反应和 Western blot 分析检测 miR-141-3p、DOK5 及 MAPK 信号通路相关基因和蛋白的表达。采用 Matrigel 血管生成和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法检测视网膜血管上皮细胞和 RGC 增殖、管腔形成和凋亡。此外，GSE2378 和 GSE9944 芯片共获得 63 个和 294 个差异表达基因，芯片中有 4 个基因存在交集。此外，结果表明 miR-141-3p 可抑制 DOK5 基因并激活 MAPK 通路。RGC 数量减少，p38、细胞外信号调节激酶 (ERK)、c-Jun 氨基末端激酶 (JNK)、IGF-1、VEGF、HIF1-α、Bax、caspase-3 表达减少，p38、ERK、JNK 磷酸化程度降低，miR-141-3p 表达上调。最后，研究结果表明，miR-141-3p 通过抑制 DOK5 介导的 MAPK 信号通路的激活抑制青光眼小鼠视网膜新生血管形成。该研究表明，miR-141-3p 通过抑制 DOK5 介导的 MAPK 信号通路的激活抑制青光眼小鼠视网膜新生血管形成。
