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
Ross CaganMount Sinai School of Medicine
Katalin SusztakUniversity of Pennsylvania