title: Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.
abstract: The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives.
authors: Escuela de Medicina. Facultad de Ciencias Médicas. Universidad de Guayaquil. Guayaquil, Guayas (Ecuador).
authors: Katherine
authors: K
authors: Carranza
authors: Escuela de Trabajo Social. Facultad de Derecho y Ciencias Sociales. Universidad Nacional de Córdoba. Córdoba (Argentina).
authors: Dolores
authors: D
authors: Veron
authors: Facultad de Ciencias de la Salud. Universidad Estatal de Milagro. Milagro, Guayas (Ecuador).
authors: Alicia
authors: A
authors: Cercado
authors: Facultad de Ciencias de la Salud. Universidad Estatal de Milagro. Milagro, Guayas (Ecuador).
authors: Noemi
authors: N
authors: Bautista
authors: Facultad de Ciencias Naturales. Universidad de Guayaquil. Guayaquil, Guayas (Ecuador).
authors: Wilson
authors: W
authors: Pozo
authors: Department of Pediatrics. Yale University y School of Medicine. New Haven, Connecticut (USA).
authors: Alda
authors: A
authors: Tufro
authors: Facultad de Ciencias de la Salud. Universidad Estatal de Milagro. Milagro, Guayas (Ecuador). Electronic address: delveron@gmail.com.
authors: Delma
authors: D
authors: Veron
mesh_terms: D042682:Angiopoietins / Q000502:physiology; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014943:Global Health; D006801:Humans; D007333:Insulin Resistance; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D011972:Receptor, Insulin / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D042682:Angiopoietins; D008565:Membrane Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C113267:nephrin; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D011972:Receptor, Insulin; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Diabetes mellitus; Diabetic nephropathy; Endotelio; Endothelium; Insulin receptor; Insulin resistance; Insulinorresistencia; Nefropatía diabética; Nitric oxide; Podocito; Podocyte; Receptor de insulina; Receptores de VEGF; South America; Sudamérica; VEGF receptor; VEGF-A; Óxido nítrico