Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide. VEGF-A is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, and both VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms worsen diabetic nephropathy. We examined the vasculoprotective effects of the anti-angiogenic VEGF-A isoform VEGF-A165b in diabetic nephropathy. VEGF-A165b was upregulated in diabetic individuals with well-preserved kidney function, but not in those with progressive disease. VEGF-A165b overexpression in mouse podocytes in vivo prevented functional and histological abnormalities in diabetic nephropathy. Systemic VEGF-A165b injections, before and after the onset of kidney disease, reduced features of diabetic nephropathy in models of both type 1 and type 2 diabetes. VEGF-A165b normalised glomerular permeability through phosphorylation of VEGFR2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A165b also improved the permeability function of diabetic human glomeruli. These results show that VEGF-A165b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, SA109
Research Symposium: Vascular Endothelial Growth Factor (VEGF-A)165b is protective in diabetic nephropathy
Y. Qiu1, S. Oltean1, J. K. Ferguson1, M. Stevens1, C. Neal1, S. C. Satchell2, S. J. Harper1, D. O. Bates3, A. J. Salmon1,2
1. School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom. 2. Academic Renal Unit, School of Clinical Science, University of Bristol, Bristol, United Kingdom. 3. Cancer Biology, Division of Oncology, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.