MicroRNA-135b-5p promotes endothelial cell proliferation and angiogenesis in diabetic retinopathy mice by inhibiting Von Hipp-el-Lindau and elevating hypoxia inducible factor α expression

Objective: This study was performed to investigate the effect of microRNA-135b-5p (miR-135b-5p) on endothelial cell proliferation and angiogenesis in diabetic retinopathy (DR) mice with the involvement of Von Hipp-el-Lindau protein (VHL) and hypoxia-inducible factor 1 α (HIF1α).Methods: A DR mouse model was established. The loss- and gain-of-function approaches were conducted to figure out the roles of miR-135b-5p and VHL in vascular hyperplasia, inflammation and apoptosis in DR mice. Endothelial cells were extracted from DR mice and transfected with miR-135b-5p- and VHL-related oligonucleotides and plasmids to decode their functions in cell viability, migration, and tube formation in DR. miR-135b-5p, VHL and HIF-1α expression in mouse retinal tissues and endothelial cells were detected. The targeting connection between miR-135b-5p and VHL was tested.Results: Elevated miR-135b-5p and HIF-1α, as well as declined VHL existed in DR. Declined miR-135b-5p or overexpressed VHL impaired vascular hyperplasia, inflammation and apoptosis, and decreased HIF-1α expression in DR mice. Repressed miR-135b-5p or up-regulated VHL inhibited viability, migration and tube formation of endothelial cells in DR. miR-135b-5p targeted VHL.Conclusion: MiR-135b-5p inhibits VHL and elevates HIF1α expression, thereby promoting endothelial cell proliferation and angiogenesis in DR mice.

Keywords: Angiogenesis; Diabetic retinopathy; Endothelial cell; Hypoxia-inducible factor 1 α; MicroRNA-135b-5p; Proliferation; Von Hipp-el-Linda.