ArticleThe American journal of pathology2012
Fibrin(ogen)-independent role of plasminogen activators in acetaminophen-induced liver injury.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Role of the Plasminogen Activation System in Liver Injury and Repair: Knowns and Known Unknowns.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism.Blood · 2025Observational
- Integrated cross-linking by TG2 and FXIII generates hepatoprotective fibrin(ogen) deposits in injured liver.Blood · 2025Article
- Degradation rather than disassembly of necrotic debris is essential to enhance recovery after acute liver injury.Cellular and molecular life sciences : CMLS · 2025Article
- Prognostic nomogram based on coagulation for individualized prediction after radical resection of hepatocellular carcinoma.European journal of medical research · 2025Article
- The C3/C3aR pathway exacerbates acetaminophen-induced mouse liver injury via upregulating podoplanin on the macrophage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease.Research and practice in thrombosis and haemostasis · 2025Article
- Acetaminophen Overdose Reveals PAR4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Fibrinolysis-Mediated Pathways in Acute Liver Injury.Seminars in thrombosis and hemostasis · 2024Review
- Targeting cathepsin C ameliorates murine acetaminophen-induced liver injury.Theranostics · 2024Article
- Robust coagulation activation and coagulopathy in mice with experimental acetaminophen-induced liver failure.Journal of thrombosis and haemostasis : JTH · 2023Article
- Altered fibrinogen γ-chain cross-linking in mutant fibrinogen-γJournal of thrombosis and haemostasis : JTH · 2023Article
- Thrombin generation assays are versatile tools in blood coagulation analysis: A review of technical features, and applications from research to laboratory routine.Journal of thrombosis and haemostasis : JTH · 2021Review
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- Review
- Mechanisms and biomarkers of liver regeneration after drug-induced liver injury.Advances in pharmacology (San Diego, Calif.) · 2019Review
- Excessive Plasmin Compromises Hepatic Sinusoidal Vascular Integrity After Acetaminophen Overdose.Hepatology (Baltimore, Md.) · 2018Article
- Plasminogen Activator Inhibitor-1 Reduces Tissue-Type Plasminogen Activator-Dependent Fibrinolysis and Intrahepatic Hemorrhage in Experimental Acetaminophen Overdose.The American journal of pathology · 2018Article
- Plasminogen Activator Inhibitor-1 Is Critical in Alcohol-Enhanced Acute Lung Injury in Mice.American journal of respiratory cell and molecular biology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatic fibrin(ogen) has been noted to occur after acetaminophen (APAP)-induced liver injury in mice. Deficiency in plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of fibrinolysis, increases APAP-induced liver injury in mice. However, the roles of fibrinogen and fibrinolysis in APAP-induced liver injury are not known. We tested the hypothesis that hepatic fibrin(ogen) deposition reduces severity of APAP-induced liver injury. APAP-induced (300 mg/kg) liver injury in mice was accompanied by thrombin generation, consumption of plasma fibrinogen, and deposition of hepatic fibrin. Neither fibrinogen depletion with ancrod nor complete fibrinogen deficiency [via knockout of the fibrinogen alpha chain gene (Fbg(-/-))] affected APAP-induced liver injury. PAI-1 deficiency (PAI-1(-/-)) increased APAP-induced liver injury and hepatic fibrin deposition 6 hours after APAP administration, which was followed by marked hemorrhage at 24 hours. As in PAI-1(-/-) mice, administration of recombinant tissue plasminogen activator (tenecteplase, 5 mg/kg) worsened APAP-induced liver injury and hemorrhage in wild-type mice. In contrast, APAP-induced liver injury was reduced in both plasminogen-deficient mice and in wild-type mice treated with tranexamic acid, an inhibitor of plasminogen activation. Activation of matrix metalloproteinase 9 (MMP-9) paralleled injury, but MMP-9 deficiency did not affect APAP-induced liver injury. The results indicate that fibrin(ogen) does not contribute to development of APAP-induced liver injury and suggest rather that plasminogen activation contributes to APAP-induced liver injury.
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Registered trials
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