PAI-1 deficiency reduces liver fibrosis after bile duct ligation in mice through activation of tPA.

Abstract:

:Plasminogen activator inhibitor-1 (PAI-1) increases injury in several liver, lung and kidney disease models. The objective of this investigation was to assess the effect of PAI-1 deficiency on cholestatic liver fibrosis and determine PAI-1 influenced fibrogenic mechanisms. We found that PAI-1(-/-) mice had less fibrosis than wild type (WT) mice after bile duct ligation. This change correlated with increased tissue-type plasminogen activator (tPA) activity, and increased matrix metalloproteinase-9 (MMP-9), but not MMP-2 activity. Furthermore, there was increased activation of the tPA substrate hepatocyte growth factor (HGF), a known anti-fibrogenic protein. In contrast, there was no difference in hepatic urokinase plasminogen activator (uPA) or plasmin activities between PAI-1(-/-) and WT mice. There was also no difference in the level of transforming growth factor beta 1 (TGF-beta1), stellate cell activation or collagen production between WT and PAI-1(-/-) animals. In conclusion, PAI-1 deficiency reduces hepatic fibrosis after bile duct obstruction mainly through the activation of tPA and HGF.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Wang H,Zhang Y,Heuckeroth RO

doi

10.1016/j.febslet.2007.05.049

subject

Has Abstract

pub_date

2007-06-26 00:00:00

pages

3098-104

issue

16

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(07)00583-2

journal_volume

581

pub_type

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