YAP1 is required for the angiogenesis in retinal microvascular endothelial cells via the inhibition of MALAT1-mediated miR-200b-3p in high glucose-induced diabetic retinopathy.

Abstract

Diabetic retinopathy (DR) is one of the severest complications in the development of diabetes with a characteristic of intraretinal new vessel formation. Our present study attempts to probe into the involvement of Yes-associated protein 1 (YAP1) in retinal microvascular endothelial cells (RMECs) and the underlying mechanism. The DR mouse model was induced by streptozotocin injection and a high-glucose/high-fat diet. After that, with the utilization of the Pearson's correlation analysis, the correlation between YAP1 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was analyzed. The relationship between microRNA-200b-3p (miR-200b-3p) and MALAT1 or vascular endothelial growth factor A (VEGFA) was then validated. Finally, the cellular processes including the abilities of proliferation, migration, as well as tube formation, were evaluated after the alteration of YAP1, MALAT1, and miR-200b-3p expression. YAP1 was observed to be highly expressed in retinas from DR mice, which promoted the cellular processes of RMECs through upregulating the MALAT1 expression. It was further confirmed that MALAT1 could sponge miR-200b-3p, and miR-200b-3p directly targeted VEGFA. When YAP1 was silenced, the RMEC proliferation, migration, and angiogenesis in the retina of DR mice were reduced. From these data, we conclude that YAP1 may exert some promotive effects on the development of DR through its regulation of the MALAT1/miR-200b-3p/VEGFA axis, highlighting that YAP1 silencing may be instrumental for the therapeutic targeting of DR.