Urokinase and its receptors in chronic kidney disease.
This review focuses on the role of the serine protease urokinase-type plasminogen activator and its high affinity receptor uPAR/CD87 in chronic kidney disease (CKD) progression. An emerging theme is their organ- and site-specific effects. In addition to tubules, uPA is produced by macrophages and fibroblasts in CKD. By activating hepatocyte growth factor and degrading fibrinogen uPA may have anti-fibrotic effects. However renal fibrosis was similar between uPA wild-type and knockout mice in experimental CKD. The uPAR is expressed by renal parenchymal cells and inflammatory cells in a variety of kidney diseases. Such expression appears anti-fibrotic based on studies in uPAR-deficient mice. In CKD uPAR expression is associated with higher uPA activity but its most important effect appears to be due to effects on cell recruitment and migration that involve interactions with a variety of co-receptors and chemoattractant effects of soluble uPAR. Vitronectin and high molecular weight kininogen are alternate uPAR ligands, and receptors in addition to uPAR may also bind directly to uPA and activate cell signaling pathways.
Zhang
Guoqiang
G
University of Washington and Children's Hospital and Regional Medical Center, Division of Nephrology, 4800 Sand Point Way NE, Seattle, WA 98105, USA.
Eddy
Allison A
AA
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D007674:Kidney Diseases / Q000201:enzymology*; D007676:Kidney Failure, Chronic / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator