Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors

Retinal hypoxia is one of the causative factors of diabetic retinopathy, and is also well-known trigger of VEGF release in diabetic retinopathy. We hypothesized that specific dysregulated miRNAs in diabetic retinopathy could be linked to hypoxia-induced damage in human retinal endothelial cells (HRECs). We investigated in HRECs the effects of chemical (CoCl2) hypoxia on the expression of HIF-1α, VEGF, PlGF, and pattern expression of a focused set of miRNAs in HREC. We found that miR-20a-5p, miR-20b-5p, miR-27a-3p, miR-27b-3p, miR-206-3p, miR-381-3p correlated also with expression of TGFβ signaling pathway genes in HRECs, challenged with chemical hypoxic stimuli. In conclusion, our data suggest that retinal angiogenesis would be promoted, at least in early phases, by up-regulation of PlGF and other factors elicited by HIF-1α such as miRNAs, VEGFA and TGFβ1.