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Publication

Diet-Induced Podocyte Dysfunction in Drosophila and Mammals.

Authors Na J, Sweetwyne MT, Park AS, Susztak K, Cagan RL Submitted By Ross Cagan on 8/4/2015 Status Published Journal Cell reports Year 2015 Date Published 7/28/2015 Volume : Pages 12 : 636 - 647 PubMed Reference 26190114 Abstract Diabetic nephropathy is a major cause of end-stage kidney disease. Characterized by progressive microvascular disease, most efforts have focused on injury to the glomerular endothelium. Recent work has suggested a role for the podocyte, a highly specialized component of the glomerular filtration barrier. Here, we demonstrate that the Drosophila nephrocyte, a cell analogous to the mammalian podocyte, displays defects that phenocopy aspects of diabetic nephropathy in animals fed chronic high dietary sucrose. Through functional studies, we identify an OGT-Polycomb-Knot-Sns pathway that links dietary sucrose to loss of the Nephrin ortholog Sns. Reducing OGT through genetic or drug means is sufficient to rescue loss of Sns, leading to overall extension of lifespan. We demonstrate upregulation of the Knot ortholog EBF2 in glomeruli of human diabetic nephropathy patients and a mouse ob/ob diabetes model. Furthermore, we demonstrate rescue of Nephrin expression and cell viability in ebf2(-/-) primary podocytes cultured in high glucose.

Investigators with authorship
Name Institution Ross Cagan Mount Sinai School of Medicine Katalin Susztak University of Pennsylvania

Complications
All ComplicationsBioinformatics BoneCardiomyopathy CardiovascularGastro-Intestinal (GI) NephropathyNeuropathy & Neurocognition Pediatric Endocrinology Retinopathy UropathyWound Healing