Journal article

Modification of kidney barrier function by the urokinase receptor

Changli Wei, Clemens C Moeller, Mehmet M Altintas, Jing Li, Karin Schwarz, Serena Zacchigna, Liang Xie, Anna Henger, Holger Schmid, Maria P Rastaldi, Peter Cowan, Matthias Kretzler, Roberto Parrilla, Se Bendayan, Vineet Gupta, Boris Nikolic, Raghu Kalluri, Peter Carmeliet, Peter Mundel, Jochen Reiser

NATURE MEDICINE | NATURE PUBLISHING GROUP | Published : 2008

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 ..

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