Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte
(pro)renin receptor expression.
Authors Cheng H, Fan X, Moeckel GW, Harris RC
Submitted By Raymond Harris on 2/22/2012
Status Published
Journal Journal of the American Society of Nephrology : JASN
Year 2011
Date Published 7/1/2011
Volume : Pages 22 : 1240 - 1251
PubMed Reference 21737546
Abstract Diabetic nephropathy (DN) increases podocyte cyclooxygenase-2 (COX-2)
expression, and COX-2 inhibition reduces proteinuria and glomerular injury in
animal models of diabetes. To investigate the role of podocyte COX-2 in
development of diabetic nephropathy, we employed a streptozotocin model of
diabetic mellitus in wild-type and transgenic mice expressing COX-2 selectively
in podocytes. Progressive albuminuria developed only in diabetic COX-2
transgenic mice despite hyperglycemia, BP, and GFR being similar to those in
wild-type mice. Transgenic mice also manifested significant foot-process
effacement, moderate mesangial expansion, and segmental thickening of the
glomerular basement membrane. In cultured podocytes overexpressing COX-2, high
glucose induced cell injury and increased both expression of the pro(renin)
receptor and activation of the renin-angiotensin system. Downregulation of the
(pro)renin receptor attenuated the injury induced by high glucose. In vivo,
podocyte pro(renin) receptor expression increased in diabetic COX-2-transgenic
mice, and treatment with a COX-2 inhibitor abrogated the upregulation of
(pro)renin receptor and reduced albuminuria, foot-process effacement, and
mesangial matrix expansion. In summary, these results demonstrate that increased
expression of podocyte COX-2 predisposes to diabetic glomerular injury and that
the (pro)renin receptor may be one mediator for this increased susceptibility to
injury.


Investigators with authorship
NameInstitution
Raymond HarrisVanderbilt University

Complications