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

Francesca Lazzara; Maria Consiglia Trotta; Chiara Bianca Maria Platania; Michele D'Amico; Francesco Petrillo; Marilena Galdiero; Carlo Gesualdo; Settimio Rossi; Filippo Drago; Claudio Bucolo

doi:10.3389/fphar.2020.01063

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

Front Pharmacol. 2020 Jul 17:11:1063. doi: 10.3389/fphar.2020.01063. eCollection 2020.

Affiliations

¹ Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
² Department of Experimental Medicine, Division of Pharmacology, University of Campania "Luigi Vanvitelli", Naples, Italy.
³ Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
⁴ Center for Research in Ocular Pharmacology-CERFO, University of Catania, Catania, Italy.

Abstract

Retinal hypoxia is one of the causative factors of diabetic retinopathy and is also one of the triggers of VEGF release. 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 of a focused set of miRNAs. 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 under HIF-1α activation, by upregulation of PlGF and other factors such as miRNAs, VEGFA, and TGFβ1.

Keywords: diabetic retinopathy; hypoxia-inducible-factor-1α; inflammation; retina; transforming growth factor beta; vascular endothelial growth factor.