Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130041, PR China.
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130041, PR China.
Cell Signal. 2020 Jul;71:109570. doi: 10.1016/j.cellsig.2020.109570. Epub 2020 Feb 19.
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.
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.
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.
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.
病理性视网膜新生血管是一种以视网膜异常血管生成为特征的疾病，是人类失明的主要原因。先前的报告强调了 microRNAs (miRNAs) 在视网膜血管生成中的作用。因此，我们旨在探讨 miR-203 调节病理性视网膜新生血管进展的机制。
首先建立病理性视网膜新生血管疾病的小鼠模型，并生成缺氧诱导的人视网膜微血管内皮细胞（HRMECs）。然后，检测 HRMECs 和视网膜组织中 miR-203 和 SNAI2 的表达。随后，研究 miR-203 和 SNAI2 对 HRMECs 活力、迁移、凋亡和血管生成的影响，并测量 Bax、Ki-67、MMP-2、MMP-9、VEGF 和 CD34 的表达。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 通路的调节作用。
病理性视网膜新生血管的 HRMECs 和视网膜组织中 miR-203 表达下调，SNAI2 表达上调。过表达 miR-203 或沉默 SNAI2 可抑制 HRMECs 的活力、迁移和血管生成，但促进细胞凋亡，表现为 Bax 表达上调，Ki-67、MMP-2、MMP-9、VEGF 和 CD34 表达下调。此外，过表达 miR-203 可通过下调 SNAI2 抑制 GSK-3β/β-catenin 通路。
综上所述，本研究表明，过表达 miR-203 通过抑制 SNAI2 使 GSK-3β/β-catenin 通路失活，从而抑制病理性视网膜新生血管疾病小鼠的血管生成，为病理性视网膜新生血管疾病提供了新的治疗思路。
