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Transcriptional profiling after bile duct ligation identifies PAI-1 as a contributor to cholestatic injury in mice by Hongtao Wang; Bhupinder P.S. Vohra; Yan Zhang; Robert O. Heuckeroth is a Medicine article available to read on EtoBox.

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Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice after BDL. PAI-1-/- mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1-/- mice had higher levels of tPA activation and mature hepatocyte growth fa

Who reads Transcriptional profiling after bile duct ligation identifies PAI-1 as a contributor to cholestatic injury in mice?

Author

Hongtao Wang; Bhupinder P.S. Vohra; Yan Zhang; Robert O. Heuckeroth

Publisher

Ovid Technologies (Wolters Kluwer Health)

Published

2005

Language

EN

Field

Medicine (Health Sciences)