Title: Modification of kidney barrier function by the urokinase receptor
Authors: Wei, Changli
Möller, Clemens C
Altintas, Mehmet M
Schwarz, Karin
Zacchigna, Serena
Xie, Liang
Henger, Anna
Schmid, Holger
Rastaldi, Maria P
Cowan, Peter
Kretzler, Matthias
Parrilla, Roberto
Bendayan, Moïse
Gupta, Vineet
Nikolic, Boris
Kalluri, Raghu
Carmeliet, Peter
Mundel, Peter
Reiser, Jochen # ×
Issue Date: Jan-2008
Publisher: Nature Pub. Co.
Series Title: Nature Medicine vol:14 issue:1 pages:55-63
Abstract: Podocyte dysfunction, represented by foot process effacement and proteinuria, is often the starting point for progressive kidney disease. Therapies aimed at the cellular level of the disease are currently not available. Here we show that induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via a mechanism that includes lipid-dependent activation of alphavbeta3 integrin. Mice lacking uPAR (Plaur-/-) are protected from lipopolysaccharide (LPS)-mediated proteinuria but develop disease after expression of a constitutively active beta3 integrin. Gene transfer studies reveal a prerequisite for uPAR expression in podocytes, but not in endothelial cells, for the development of LPS-mediated proteinuria. Mechanistically, uPAR is required to activate alphavbeta3 integrin in podocytes, promoting cell motility and activation of the small GTPases Cdc42 and Rac1. Blockade of alphavbeta3 integrin reduces podocyte motility in vitro and lowers proteinuria in mice. Our findings show a physiological role for uPAR signaling in the regulation of kidney permeability.
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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