BACKGROUND Pathological retinal neovascularization is a disease characterized by abnormal angiogenesis in retina that is a major cause of blindness in humans. Previous reports have highlighted the involvement of microRNAs (miRNAs) in retinal angiogenesis. Therefore, we aimed at exploring the mechanism underlying miR-203 regulating the progression of pathological retinal neovascularization. METHODS Initially, the mouse model of pathological retinal neovascularization disease was established and the hypoxia-induced human retinal microvascular endothelial cells (HRMECs) were generated. Then, miR-203 and SNAI2 expression in HRMECs and retinal tissues was examined. Subsequently, the effects of miR-203 and SNAI2 on viability, migration, apoptosis and angiogenesis of HRMECs were investigated, with the expression of Bax, Ki-67, MMP-2, MMP-9, VEGF and CD34 measured. Finally, the regulation of miR-203 or SNAI2 on GSK-3β/β-catenin pathway was determined through examining the levels of phosphorylated p-GSK-3β and β-catenin. RESULTS Poorly expressed miR-203 and highly expressed SNAI2 were found in HRMECs and retinal tissues of pathological retinal neovascularization. Importantly, overexpressed miR-203 or silencing SNAI2 inhibited viability, migration and angiogenesis but promoted apoptosis of HRMECs, evidenced by elevated Bax expression but reduced expression of Ki-67, MMP-2, MMP-9, VEGF and CD34. Moreover, overexpression of miR-203 was found to repress the GSK-3β/β-catenin pathway by downregulating SNAI2. CONCLUSION Collectively, this study demonstrated that overexpression of miR-203 suppressed the angiogenesis in mice with pathological retinal neovascularization disease via the inactivation of GSK-3β/β-catenin pathway by inhibiting SNAI2, which provided a novel therapeutic insight for pathological retinal neovascularization disease.

中文翻译：

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miR-203 通过下调 SNAI2 在患有病理性视网膜新生血管疾病的小鼠血管生成中的抑制作用。

背景病理性视网膜新生血管形成是一种以视网膜血管生成异常为特征的疾病，是人类失明的主要原因。以前的报告强调了微 RNA (miRNA) 在视网膜血管生成中的参与。因此，我们旨在探索miR-203调控病理性视网膜新生血管化进程的机制。方法首先建立病理性视网膜新生血管病小鼠模型，制备缺氧诱导的人视网膜微血管内皮细胞（HRMECs）。然后，检查了 HRMEC 和视网膜组织中 miR-203 和 SNAI2 的表达。随后，研究了 miR-203 和 SNAI2 对 HRMECs 活力、迁移、凋亡和血管生成的影响，其中 Bax、Ki-67、MMP-2、MMP-9、测量VEGF和CD34。最后，通过检测磷酸化 p-GSK-3β 和 β-catenin 的水平，确定 miR-203 或 SNAI2 对 GSK-3β/β-catenin 通路的调控。结果在病理性视网膜新生血管的HRMECs和视网膜组织中发现miR-203低表达和SNAI2高表达。重要的是，过表达的 miR-203 或沉默 SNAI2 会抑制活力、迁移和血管生成，但会促进 HRMEC 的凋亡，这可以通过 Bax 表达升高但 Ki-67、MMP-2、MMP-9、VEGF 和 CD34 表达降低来证明。此外，发现 miR-203 的过表达通过下调 SNAI2 来抑制 GSK-3β/β-catenin 通路。结论 总的来说，