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Urokinase-type Plasminogen Activator Supports Liver Repair Independent of Its Cellular Receptor by Kumar Shanmukhappa; Gregg E Sabla; Jay L Degen; Jorge A Bezerra is a Medicine article available to read on EtoBox.

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## Background The urokinase-type (uPA) and tissue-type (tPA) plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen (Plg) to the active protease plasmin. Based on the efficient activation of plasminogen when uPA is bound to its receptor (uPAR) and on the role of uPA in plasmin-mediated liver repair, we hypothesized that uPA requires uPAR for efficient liver repair. ## Methods To test this hypothesis, we administered one dose of carbon tetrachloride (CCl~4~) to mice with single or combined deficiencies of uPA, uPAR and tPA, and examined hepatic morphology, cellular proliferation, fibrin clearance, and hepatic proteolysis 2–14 days later. ## Results Absence of uPAR alone or the combined absence of uPAR and tPA had no impact on the resolution of centrilobular injury, but the loss of receptor-free uPA significantly impaired the clearance of necrotic hepatocytes up to 14 days after CCl~4~. In response to the injury, hepatocyte proliferation was normal in mice of all genotypes, except for uPAR-deficient (uPAR°) mice, which had a reproducible but mild decrease by 33% at day 2, with an appropriate restoration of liver mass by 7 days similar to experi

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Author

Kumar Shanmukhappa; Gregg E Sabla; Jay L Degen; Jorge A Bezerra

Publisher

BioMed Central; Springer (Biomed Central Ltd.); London: BioMed Central, 2001-; Springer Science and Business Media LLC; Society for Mining, Metallurgy and Exploration Inc. (ISSN 1471-230X)

Published

2006

Language

EN

Field

Medicine (Health Sciences)