Cited by 102Liver physiology and pathologyLiver Diseases and ImmunityLiver Disease Diagnosis and Treatment

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

Wang, Hongtao, Zhang, Yan, Heuckeroth, Robert O.·2007·FEBS Letters

DOI 10.1016/j.febslet.2007.05.049

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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‐β1), 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.

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Additional file 3 of Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches
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Additional file 4 of Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches
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A new role for tissue-type plasminogen activator in liver injury
Kang, L. (2013) · D-Scholarship@Pitt (University of Pittsburgh)

Authors: Wang, H., Zhang, Y., & Heuckeroth, R. O.
Affiliations: Washington University in St. Louis (US)
Sun Yat-sen University (CN)
Corresponding author: Heuckeroth, Robert O.
ORCID: Wang, Hongtao
Zhang, Yan
Heuckeroth, Robert O.
Venue: FEBS Letters
Publisher: Wiley
Published: 2007-05-29
Volume: 581
Issue: 16
Pages: 3098-3104
ISSN: 0014-5793 (ISSN-L)
1873-3468
DOI: 10.1016/j.febslet.2007.05.049
OpenAlex: W1970138640
Cited by: 98
References: 35
Citations by year: 2026: 4 · 2025: 8 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 3 · 2014: 7 · 2013: 9 · 2012: 5
FWCI: 3.65
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: FEBS Letters (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1c06rr015502-01)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 068371, P30 DK-52574, R01DK064592, DK 64592, DK62452, R01DK057038, R21DK068371, DK57038, U01DK062452, P30DK056341, P30DK052574)
National Center for Research Resources (C06-RR-015502)
Topics: Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Keywords: plasminogen activator inhibitor-1, liver fibrosis, bile duct ligation, cholestasis, tissue plasminogen activator, hepatocyte growth factor, MMP-9, urokinase, plasmin, hepatic stellate cells, TGF-β1
MeSH terms: Animals, Bile Ducts, Fibrinolysin, Ligation, Liver, Liver Cirrhosis, Male, Mice, Inbred C57BL, Tissue Plasminogen Activator, Urokinase-Type Plasminogen Activator, Hepatocyte Growth Factor, Plasminogen Activator Inhibitor 1, Mice, Knockout, Matrix Metalloproteinase 9, Mice, Transforming Growth Factor beta1

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

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