ArticleJournal of thrombosis and haemostasis : JTH2015
Coagulation-driven platelet activation reduces cholestatic liver injury and fibrosis in mice.
Article in Journal of thrombosis and haemostasis : JTH, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
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- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
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- Altered fibrinogen γ-chain cross-linking in mutant fibrinogen-γJournal of thrombosis and haemostasis : JTH · 2023Article
- Targeting endothelial coagulation signaling ameliorates liver obstructive cholestasis and dysfunctional angiogenesis.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Microvascular Thrombosis and Liver Fibrosis Progression: Mechanisms and Clinical Applications.Cells · 2023Review
- Mesenchymal Stem/Stromal Cells in Progressive Fibrogenic Involvement and Anti-Fibrosis Therapeutic Properties.Frontiers in cell and developmental biology · 2022Review
- Von Willebrand factor exerts hepatoprotective effects in acute but not chronic cholestatic liver injury in mice.Toxicology · 2021Article
- Advances in functional and molecular MRI technologies in chronic liver diseases.Journal of hepatology · 2020Review
- Liver fibrosis is driven by protease-activated receptor-1 expressed by hepatic stellate cells in experimental chronic liver injury.Research and practice in thrombosis and haemostasis · 2020Article
- Molecular Magnetic Resonance Imaging of Fibrin Deposition in the Liver as an Indicator of Tissue Injury and Inflammation.Investigative radiology · 2020Article
- Hepatic Surgical Stress Promotes Systemic Immunothrombosis That Results in Distant Organ Injury.Frontiers in immunology · 2020Article
- Intrahepatic fibrin(ogen) deposition drives liver regeneration after partial hepatectomy in mice and humans.Blood · 2019Article
- Review
- Chronic liver injury drives non-traditional intrahepatic fibrin(ogen) crosslinking via tissue transglutaminase.Journal of thrombosis and haemostasis : JTH · 2019Article
- Role of the blood coagulation cascade in hepatic fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2018Review
- Platelets as Modulators of Liver Diseases.Seminars in thrombosis and hemostasis · 2018Review
- Effects of human amnion-derived mesenchymal stem cells and conditioned medium in rats with sclerosing cholangitis.American journal of translational research · 2018Article
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9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe coagulation cascade has been shown to participate in chronic liver injury and fibrosis, but the contribution of various thrombin targets, such as protease activated receptors (PARs) and fibrin(ogen), has not been fully described. Emerging evidence suggests that in some experimental settings of chronic liver injury, platelets can promote liver repair and inhibit liver fibrosis. However, the precise mechanisms linking coagulation and platelet function to hepatic tissue changes following injury remain poorly defined.
objectivesTo determine the role of PAR-4, a key thrombin receptor on mouse platelets, and fibrin(ogen) engagement of the platelet αII b β3 integrin (αIIb β3 ) in a model of cholestatic liver injury and fibrosis.
methodsBiliary and hepatic injury was characterized following 4 week administration of the bile duct toxicant α-naphthylisothiocyanate (ANIT) (0.025%) in PAR-4-deficient mice, mice expressing a mutant form of fibrin(ogen) incapable of binding integrin αII b β3 (Fibγ(Δ5) ), and wild-type mice.
resultsElevated plasma thrombin-antithrombin and serotonin levels, hepatic fibrin deposition, and platelet accumulation in liver accompanied hepatocellular injury and fibrosis in ANIT-treated wild-type mice. PAR-4 deficiency reduced plasma serotonin levels, increased serum bile acid concentration, and exacerbated ANIT-induced hepatocellular injury and peribiliary fibrosis. Compared with PAR-4-deficient mice, ANIT-treated Fibγ(Δ5) mice displayed more widespread hepatocellular necrosis accompanied by marked inflammation, robust fibroblast activation, and extensive liver fibrosis.
conclusionsCollectively, the results indicate that PAR-4 and fibrin-αII b β3 integrin engagement, pathways coupling coagulation to platelet activation, each exert hepatoprotective effects during chronic cholestasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.