Inhibitory role of miR-203 in the angiogenesis of mice with pathological retinal neovascularization disease through downregulation of SNAI2

Li Yu  ¹ , Shuai Wu  ¹ , Songtian Che  ¹ , Yazhen Wu  ¹ , Ning Han  ² Affiliations

• PMID: 32084532
• DOI: 10.1016/j.cellsig.2020.109570

Abstract

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.

Keywords: Angiogenesis; GSK-3β/β-catenin pathway; Pathological retinal neovascularization; SNAI2; microRNA-203.