title: Nap Interferes with Hypoxia-Inducible Factors and VEGF Expression in Retina of Diabetic Rats.
abstract: The retinal microvascular damage is a complication of diabetic retinopathy (DR). Hyperglycemia and hypoxia are responsible of aberrant vessel's proliferation. The cellular response to hypoxia is mediated through activation of hypoxia-inducible factors (HIFs). Among these, HIF-1α modulates expression of its target gene, VEGF, whose upregulation controls the angiogenic event during DR development. In a previous study, we have demonstrated that a small peptide, NAP, is able to protect retina from hyperglycemic insult. Here, we have demonstrated that its intraocular administration in a rat model of diabetic retinopathy has reduced expression of HIF-1α, HIF-2α, and VEGF by increasing HIF-3α levels. These data have been also confirmed by immunolocalization study by confocal microscopy. Although these evidences need to be further deepened to understand the molecular mechanism involved in the protective NAP action, the present data suggest that this small peptide may be effective to prevent the development of this ocular pathology.
authors.affiliation: San Raffaele Open University of Rome, Rome, Italy.|Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy.
authors.forename: Agata Grazia
authors.initials: AG
authors.lastname: D'Amico
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Maugeri
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bucolo
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saccone
authors.affiliation: Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Federico
authors.affiliation: Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cavallaro
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy. vdagata@unict.it.
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D056965:Injections, Intraocular; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D009842:Oligopeptides; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C497444:Hif1a protein, rat; C424683:Hif3a protein, rat; C425904:davunetide
keywords: Diabetic retinopathy; Hypoxia-inducible factors; Nap; VEGF