Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
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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.