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Vascular Endothelial Growth Factor (VEGF) in the Pathogenesis of Diabetic Nephropathy of Type 1 Diabetes Mellitus

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Diabetic nephropathy (DN) is a common complication of diabetes mellitus and is the primary cause of endstage renal disease in the Western World. Vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of DN of type 1 diabetes mellitus. VEGF is the main angiogenic factor and a potent mitogen for endothelial cells. It is mainly produced in kidney by podocytes and exerts its biological activities by binding to its receptors (VEGFRs). Alternative splicing of a single VEGF gene produces various isoforms and two families with anti- and pro-angiogenic properties. In normal glomeruli, VEGF isoforms are in tight regulation and act in a paracrine and an autocrine manner preserving the integrity of glomerular filtration barrier. Many mediators in diabetic milieu induce the expression of VEGF and possibly the VEGFxxx isoform in animal models of type 1 diabetes, however, in human kidney with developed DN, VEGF expression seems to be lower or absent. Inhibition of VEGF in experimental DN ameliorates structural and functional changes and proposes possible therapeutic targets. Further studies are required before these treatments can be used in diabetic patients at early stages of DN.

Keywords: AGEs; Aflibercept; CTAD; Denys-Drash syndrome; Diabetic nephropathy; ELISA; ERK; HIF; Nephropathy; Pegaptanib; PlGF; ROS; Rac; Ranibizumab; VEGF; VEGF Trap-Eye; VEGFRs; Vascular endothelial growth factor; albuminuria; angiogenesis; angiotensin converting enzyme (ACE); glomerular endotheliosis; glomerular filtration rate (GFR); glomerulosclerosis; hypertension; hypertrophy; microalbuminuria; nephritic syndrome; pathogenesis; proteinuria; renal hypoxia; sFlt-1; type 1 diabetes mellitus

Document Type: Research Article

Publication date: January 1, 2011

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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