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Publication - Professor Peter Mathieson

    VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy

    Citation

    Onions, K, Gamez, M, Buckner, N, Baker, S, Betteridge, K, Desideri, S, Dallyn, B, Ramnath, R, Neal, C, Farmer, L, Mathieson, P, Gnudi, L, Alitalo, K, Bates, D, Salmon, A, Welsh, G, Satchell, S & Foster, R, 2018, ‘VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy’. Diabetes.

    Abstract

    Elevated levels of vascular endothelial growth factor (VEGF)A are thought to cause glomerular endothelial cell (GEnC) dysfunction and albuminuria in diabetic nephropathy. We hypothesized that VEGFC could counteract these effects of VEGFA to protect the glomerular filtration barrier and reduce albuminuria. Isolated glomeruli were stimulated ex vivo with VEGFC, which reduced VEGFA- and type II diabetes-induced glomerular albumin permeability (Ps’alb). VEGFC had no detrimental effect on glomerular function in vivo when over-expression was induced locally in podocytes (podVEGFC) in otherwise healthy mice. Further, these mice had reduced glomerular VEGFA mRNA expression, yet increased glomerular VEGF receptor heterodimerization indicating differential signalling by VEGFC. In a model of type I diabetes, induction of podocyte VEGFC over-expression reduced the development of hypertrophy, albuminuria, loss of GEnC fenestrations and protected against altered VEGF receptor expression. In addition, VEGFC protected against raised Ps’alb by endothelial glycocalyx disruption in glomeruli. In summary VEGFC; reduced the development of diabetic nephropathy; prevented VEGF receptor alterations in the diabetic glomerulus; promoted both glomerular protection and endothelial barrier function. These important findings highlight a novel pathway for future investigation in the treatment of diabetic nephropathy.

    Full details in the University publications repository