Knockdown of Malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p/VEGF-A axis.

Abstract Diabetic retinopathy (DR), characterized by intraretinal vessel formation, is a major complication in diabetes. Neovascularization is an important characteristic of DR, but its formation mechanism remains unclear. In this research, Malat1, miR-205-5p, and VEGF-A levels in high glucose (HG) treat-human retinal microvascular endothelial cells (hRMECs) was detected with qRT-PCR. CCK-8 assay, transwell assay, and tube formation assay was applied to access hRMEC viability, migration, and angiogenesis. Expression level of endothelial-mesenchymal transition (EndMT) markers (VE-cadherin, FSP1, and α-SMA) was detected by western blotting assay. Interaction among Malat1, miR-205-5p, and VEGF-A was confirmed by dual-luciferase reporter assay. Furthermore, in vivo DR mouse model was induced, and the effect of Malat1 on DR and EndMT markers was confirmed through hematoxylin-eosin (HE) staining and western blotting. As a result, Malat1 and VEGF-A was upregulated while miR-205-5p was suppressed under HG conditions. Malat1 could sponge miR-205-5p to regulate VEGF-A expression. Malat1 knockdown inhibited hRMEC proliferation, migration, and tube formation by targeting miR-205-5p under HG conditions. Furthermore, inhibition of Malat1 prevented the HG-induced EndMT process. In summary, Malat1 knockdown diminished hRMEC dysfunctions by regulating miR-205-5p/VEGF-A, providing a useful insight for exploring new therapeutic target for DR.