ArticleJournal of cellular and molecular medicine2018
Potential role of the methylation of VEGF gene promoter in response to hypoxia in oxygen-induced retinopathy: beneficial effect of the absence of AQP4.
Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- A novel molecule ZYZ329 targeting histone methyltransferase SMYD3 suppresses pathological angiogenesis via the driven mitochondrial ROS/HIF-1α/VEGFA axis.Journal of translational medicine · 2026Article
- Recent advances in engineered exosome-based therapies for ocular vascular disease.Journal of nanobiotechnology · 2025Review
- Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.International journal of molecular sciences · 2024Review
- Natural History of Glaucoma Progression in the DBA/2J Model: Early Contribution of Müller Cell Gliosis.Cells · 2023Article
- Propranolol ameliorates retinopathy of prematurity in mice by downregulating HIF-1α via the PI3K/Akt/ERK pathway.Pediatric research · 2023Article
- Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy.International journal of molecular sciences · 2023Article
- Review
- Article
- Article
- Alteration of the translational readthrough isoform AQP4ex induces redistribution and downregulation of AQP4 in human glioblastoma.Cellular and molecular life sciences : CMLS · 2022Article
- Potential epigenetic molecular regulatory networks in ocular neovascularization.Frontiers in genetics · 2022Review
- Dose Response of Bumetanide on Aquaporins and Angiogenesis Biomarkers in Human Retinal Endothelial Cells Exposed to Intermittent Hypoxia.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Kir4.1 may represent a novel therapeutic target for diabetic retinopathy (Review).Experimental and therapeutic medicine · 2021Review
- Vegfa promoter gene hypermethylation at HIF1α binding site is an early contributor to CKD progression after renal ischemia.Scientific reports · 2021Article
- Up-regulation of pro-angiogenic pathways and induction of neovascularization by an acute retinal light damage.Scientific reports · 2020Article
- Bumetanide Suppression of Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy.International journal of molecular sciences · 2020Article
- Further understanding of epigenetic dysfunction of the retinal pigment epithelium in AMD.Expert review of ophthalmology · 2020Article
- Aquaporin 4 Suppresses Neural Hyperactivity and Synaptic Fatigue and Fine-Tunes Neurotransmission to Regulate Visual Function in the Mouse Retina.Molecular neurobiology · 2019Article
- Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells.Experimental eye research · 2019Article
- Vascular and Neuronal Protection in the Developing Retina: Potential Therapeutic Targets for Retinopathy of Prematurity.International journal of molecular sciences · 2019Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-dependent accumulation of vascular endothelial growth factor (VEGF) plays a major role in retinal diseases characterized by neovessel formation. In this study, we investigated whether the glial water channel Aquaporin-4 (AQP4) is involved in the hypoxia-dependent VEGF upregulation in the retina of a mouse model of oxygen-induced retinopathy (OIR). The expression levels of VEGF, the hypoxia-inducible factor-1α (HIF-1α) and the inducible form of nitric oxide synthase (iNOS), the production of nitric oxide (NO), the methylation status of the HIF-1 binding site (HBS) in the VEGF gene promoter, the binding of HIF-1α to the HBS, the retinal vascularization and function have been determined in the retina of wild-type (WT) and AQP4 knock out (KO) mice under hypoxic (OIR) or normoxic conditions. In response to 5 days of hypoxia, WT mice were characterized by (i) AQP4 upregulation, (ii) increased levels of VEGF, HIF-1α, iNOS and NO, (iii) pathological angiogenesis as determined by engorged retinal tufts and (iv) dysfunctional electroretinogram (ERG). AQP4 deletion prevents VEGF, iNOS and NO upregulation in response to hypoxia thus leading to reduced retinal damage although in the presence of high levels of HIF-1α. In AQP4 KO mice, HBS demethylation in response to the beginning of hypoxia is lower than in WT mice reducing the binding of HIF-1α to the VEGF gene promoter. We conclude that in the absence of AQP4, an impaired HBS demethylation prevents HIF-1 binding to the VEGF gene promoter and the relative VEGF transactivation, reducing the VEGF-induced retinal damage in response to hypoxia.
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