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 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...

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Main Authors: Francesca Lazzara, Maria Consiglia Trotta, Chiara Bianca Maria Platania, Michele D’Amico, Francesco Petrillo, Marilena Galdiero, Carlo Gesualdo, Settimio Rossi, Filippo Drago, Claudio Bucolo
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-07-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2020.01063/full
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author Francesca Lazzara
Maria Consiglia Trotta
Chiara Bianca Maria Platania
Michele D’Amico
Francesco Petrillo
Marilena Galdiero
Carlo Gesualdo
Settimio Rossi
Filippo Drago
Filippo Drago
Claudio Bucolo
Claudio Bucolo
author_facet Francesca Lazzara
Maria Consiglia Trotta
Chiara Bianca Maria Platania
Michele D’Amico
Francesco Petrillo
Marilena Galdiero
Carlo Gesualdo
Settimio Rossi
Filippo Drago
Filippo Drago
Claudio Bucolo
Claudio Bucolo
author_sort Francesca Lazzara
collection DOAJ
description 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.
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spelling doaj.art-4135089e63894410b0059896aa16590e2022-12-21T20:14:40ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-07-011110.3389/fphar.2020.01063543310Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth FactorsFrancesca Lazzara0Maria Consiglia Trotta1Chiara Bianca Maria Platania2Michele D’Amico3Francesco Petrillo4Marilena Galdiero5Carlo Gesualdo6Settimio Rossi7Filippo Drago8Filippo Drago9Claudio Bucolo10Claudio Bucolo11Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, ItalyDepartment of Experimental Medicine, Division of Pharmacology, University of Campania “Luigi Vanvitelli”, Naples, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, ItalyDepartment of Experimental Medicine, Division of Pharmacology, University of Campania “Luigi Vanvitelli”, Naples, ItalyDepartment of Experimental Medicine, Division of Pharmacology, University of Campania “Luigi Vanvitelli”, Naples, ItalyDepartment of Experimental Medicine, Division of Pharmacology, University of Campania “Luigi Vanvitelli”, Naples, ItalyEye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Naples, ItalyEye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Naples, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, ItalyCenter for Research in Ocular Pharmacology-CERFO, University of Catania, Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, ItalyCenter for Research in Ocular Pharmacology-CERFO, University of Catania, Catania, ItalyRetinal 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.https://www.frontiersin.org/article/10.3389/fphar.2020.01063/fullhypoxia-inducible-factor-1αvascular endothelial growth factortransforming growth factor betaretinadiabetic retinopathyinflammation
spellingShingle Francesca Lazzara
Maria Consiglia Trotta
Chiara Bianca Maria Platania
Michele D’Amico
Francesco Petrillo
Marilena Galdiero
Carlo Gesualdo
Settimio Rossi
Filippo Drago
Filippo Drago
Claudio Bucolo
Claudio Bucolo
Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors
Frontiers in Pharmacology
hypoxia-inducible-factor-1α
vascular endothelial growth factor
transforming growth factor beta
retina
diabetic retinopathy
inflammation
title Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors
title_full Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors
title_fullStr Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors
title_full_unstemmed Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors
title_short Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors
title_sort stabilization of hif 1α in human retinal endothelial cells modulates expression of mirnas and proangiogenic growth factors
topic hypoxia-inducible-factor-1α
vascular endothelial growth factor
transforming growth factor beta
retina
diabetic retinopathy
inflammation
url https://www.frontiersin.org/article/10.3389/fphar.2020.01063/full
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