ArticleBMC gastroenterology2018
Thrombin and factor Xa link the coagulation system with liver fibrosis.
Article in BMC gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Effects of Anticoagulants on Experimental Models of Established Chronic Liver Diseases: A Systematic Review and Meta-Analysis.Canadian journal of gastroenterology & hepatology · 2020Pooled it
- Liver Innervation in Health and Disease: Neuroimmune-Neurovascular Interface and Future Therapeutic Implications.Biomedicines · 2025Review
- Identification of novel gene expression programs in thrombin-stimulated hepatic stellate cells.Research and practice in thrombosis and haemostasis · 2025Article
- Microvesicle Tissue Factor Procoagulant Activity Is Elevated and Correlated With Disease Severity in Patients With Cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Article
- Xa inhibitor edoxaban ameliorates hepatic ischemia-reperfusion injury via PAR-2-ERK 1/2 pathway.PloS one · 2024Article
- Lysyl oxidase like-2 in fibrosis and cardiovascular disease.American journal of physiology. Cell physiology · 2023Review
- Scalable production of tissue-like vascularized liver organoids from human PSCs.Experimental & molecular medicine · 2023Article
- Targeting endothelial coagulation signaling ameliorates liver obstructive cholestasis and dysfunctional angiogenesis.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Thrombin cleavage of the hepatitis E virus polyprotein at multiple conserved locations is required for genome replication.PLoS pathogens · 2023Article
- Microvascular Thrombosis and Liver Fibrosis Progression: Mechanisms and Clinical Applications.Cells · 2023Review
- Lysyl oxidase-like 2 processing by factor Xa modulates its activity and substrate preference.Communications biology · 2023Article
- Effects of Thrombin on the Neurovascular Unit in Cerebral Ischemia.Cellular and molecular neurobiology · 2022Review
- Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysisWorld journal of gastroenterology · 2022Article
- The effects of rivaroxaban, an oral anticoagulant, on human IVD primary cultures.Archives of medical science : AMS · 2022Article
- Impact of prothrombin and factor V Leiden mutations on the progression of fibrosis in patients with chronic hepatitis C.PloS one · 2022Article
- [Pathophysiology of bleeding].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2021Review
- Dabigatran mitigates cisplatin-mediated nephrotoxicity through down regulation of thrombin pathway.Journal of advanced research · 2021Article
- Activated Blood Coagulation Factor X (FXa) Contributes to the Development of Traumatic PVR Through Promoting RPE Epithelial-Mesenchymal Transition.Investigative ophthalmology & visual science · 2021Article
- 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
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis.
methodsHSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated. C57BL/6 J mice were administered thioacetamide (TAA) for 8 weeks with Rivaroxaban (n = 15) or Dabigatran (n = 15). Control animals received TAA alone (n = 15). Fibrosis was scored and quantified using digital image analysis and hepatic tissue hydroxyproline estimated.
resultsStellate cells treated with FXa and thrombin demonstrated upregulation of procollagen, TGF-beta, αSMA and significant cell contraction (43.48%+/- 4.12) compared to culturing with FXa or thrombin alone (26.90%+/- 8.90, p = 0.02; 13.1%+/- 9.84, p < 0.001). Mean fibrosis score, percentage area of fibrosis and hepatic hydroxyproline content (2.46 vs 4.08, p = 0.008; 2.02% vs 3.76%, p = 0.012; 276.0 vs 651.3, p = 0.0001) were significantly reduced in mice treated with the FXa inhibitor compared to control mice. FXa inhibition was significantly more effective than thrombin inhibition in reducing percentage area of fibrosis and hepatic hydroxyproline content (2.02% vs 3.70%,p = 0.031; 276.0 vs 413.1,p = 0.001).
conclusionsFXa promotes stellate cell contractility and activation. Early inhibition of coagulation using a FXa inhibitor significantly reduces TAA induced murine liver fibrosis and may be a viable treatment for liver fibrosis in patients.
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Registered trials
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.