title: A polymorphism of HMGA1 protects against proliferative diabetic retinopathy by impairing HMGA1-induced VEGFA expression.
abstract: Diabetic retinopathy (DR) is a major complication of diabetes mellitus, and is the leading cause of blindness in working-age people. Usually, DR progresses from the asymptomatic non-proliferative DR that does not significantly alter vision, to proliferative DR (PDR), which can result in aberrant retinal neovessel formation and blindness. The High-Mobility-Group A1 (HMGA1) protein is a transcriptional master regulator of numerous genes, including metabolic and inflammatory genes, which, by modulating the expression of angiogenic factors, may induce retinal neovascularization, a hallmark of PDR. Herein, we examined the relationship between HMGA1 rs139876191 variant and DR. Results revealed that patients with type 2 diabetes, who were carriers of the HMGA1 rs139876191 variant had a significantly lower risk of developing PDR, compared to non-carrier diabetic patients. From a mechanistic point of view, our findings indicated that, by adversely affecting HMGA1 protein expression and function, the HMGA1 rs139876191 variant played a key role in this protective mechanism by downregulating the expression of vascular endothelial growth factor A (VEGFA), a major activator of neovascularization in DR. These data provide new insights into the pathogenesis and progression of DR, and may offer opportunities for discovering novel biomarkers and therapeutic targets for diagnosis, prevention and treatment of PDR.
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Chiefari
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ventura
authors.affiliation: Operative Unit of Endocrinology and Diabetes, Hospital Pugliese-Ciaccio, Catanzaro, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Capula
authors.affiliation: Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Randazzo
authors.affiliation: Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Scorcia
authors.affiliation: Institute of Experimental Endocrinology and Oncology, CNR, Napoli, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fedele
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Biagio
authors.initials: B
authors.lastname: Arcidiacono
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Nevolo
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Francesco Luciano
authors.initials: FL
authors.lastname: Bilotta
authors.affiliation: Institute of Experimental Endocrinology and Oncology, CNR, Napoli, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Vitiello
authors.affiliation: Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Palmieri
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Gulletta
authors.affiliation: Institute of Experimental Endocrinology and Oncology, CNR, Napoli, Italy.|Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Napoli, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Foti
authors.affiliation: Operative Unit of Endocrinology and Diabetes, Hospital Pugliese-Ciaccio, Catanzaro, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Vero
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Brunetti
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D057809:HEK293 Cells; D025741:HMGA1a Protein / Q000235:genetics*; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012160:Retina / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D025741:HMGA1a Protein