Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9188
Title: Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in experimental diabetes.
Authors: Cooper, Mark E;Vranes, D;Youssef, S;Stacker, S A;Cox, Allison J;Rizkalla, B;Casley, David J;Bach, Leon A;Kelly, D J;Gilbert, Richard E
Affiliation: cooper@austin.unimelb.edu.au
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, West Heidelberg, Victoria, Australia
Issue Date: 1-Nov-1999
Citation: Diabetes; 48(11): 2229-39
Abstract: It has been suggested that the cytokine vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of diabetic retinopathy, but its role in nephropathy has not been clearly demonstrated. Assessment of VEGF, 125I-VEGF binding, and vascular endothelial growth factor receptor-2 (VEGFR-2) in the kidney was performed after 3 and 32 weeks of streptozotocin-induced diabetes. Gene expression of both VEGF and VEGFR-2 was assessed by Northern blot analysis and the localization of the ligand and receptor was examined by in situ hybridization. VEGF and VEGFR-2 protein were also evaluated by immunohistochemistry. Binding of the radioligand 125I-VEGF was evaluated by in vitro and in vivo autoradiography. Diabetes was associated with increased renal VEGF gene expression. VEGF mRNA and protein were localized to the visceral epithelial cells of the glomerulus and to distal tubules and collecting ducts in both diabetic and nondiabetic rats. Renal VEGFR-2 mRNA was increased after 3 weeks of diabetes but not in long-term diabetes. In situ hybridization and immunohistochemical studies revealed that glomerular endothelial cells were the major site of VEGFR-2 expression. In addition, VEGFR-2 gene expression was detected in cortical and renomedullary interstitial cells and on endothelial cells of peritubular capillaries. There was an increase in 125I-VEGF binding sites after 3 but not 32 weeks of diabetes. The major VEGF binding sites were in the glomeruli. 125I-VEGF binding was also observed in medullary rays and in the renal papillae. These studies indicate an early and persistent increase in renal VEGF gene expression in association with experimental diabetes. In addition, an early and transient increase in renal VEGF receptors was also observed in diabetic rats. These findings are consistent with a role for VEGF in mediating some of the changes observed in the diabetic kidney.
Internal ID Number: 10535459
URI: http://ahro.austin.org.au/austinjspui/handle/1/9188
URL: http://www.ncbi.nlm.nih.gov/pubmed/10535459
Type: Journal Article
Subjects: Animals
Blood Glucose.metabolism
Blood Pressure
Blotting, Northern
Body Weight
Diabetes Mellitus, Experimental.genetics.metabolism.physiopathology
Endothelial Growth Factors.genetics.metabolism
Gene Expression Regulation
Immunohistochemistry
In Situ Hybridization
Kidney.metabolism
Lymphokines.genetics.metabolism
RNA, Messenger.genetics
Rats
Rats, Sprague-Dawley
Receptor Protein-Tyrosine Kinases.genetics.metabolism
Receptors, Growth Factor.genetics.metabolism
Receptors, Vascular Endothelial Growth Factor
Transcription, Genetic
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Appears in Collections:Journal articles

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