ArticleHepatology (Baltimore, Md.)2009
Fibrin accumulation plays a critical role in the sensitization to lipopolysaccharide-induced liver injury caused by ethanol in mice.
Article in Hepatology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- An updated systematic review and meta-analysis: correlation between circulating plasminogen activator inhibitor-1 levels and metabolic dysfunction-associated steatotic liver disease.BMC gastroenterology · 2025Pooled it
- Role of the Plasminogen Activation System in Liver Injury and Repair: Knowns and Known Unknowns.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Hepatic Extracellular Matrix and Its Role in the Regulation of Liver Phenotype.Seminars in liver disease · 2024Review
- Fibrinolysis-Mediated Pathways in Acute Liver Injury.Seminars in thrombosis and hemostasis · 2024Review
- Hepatic inflammatory responses in liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- The plasma degradome reflects later development of NASH fibrosis after liver transplant.Scientific reports · 2023Article
- Fibrosis resolution in the mouse liver: Role of Mmp12 and potential role of calpain 1/2.Matrix biology plus · 2023Article
- Advancements in the Alcohol-Associated Liver Disease Model.Biomolecules · 2022Review
- Simvastatin Prevents Liver Microthrombosis and Sepsis Induced Coagulopathy in a Rat Model of Endotoxemia.Cells · 2022Article
- Extrahepatic factors in hepatic immune regulation.Frontiers in immunology · 2022Review
- Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?Acta pharmaceutica Sinica. B · 2021Review
- Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis.Nature communications · 2021Article
- The liver matrisome - looking beyond collagens.JHEP reports : innovation in hepatology · 2020Review
- The Matrisome, Inflammation, and Liver Disease.Seminars in liver disease · 2020Review
- Rapamycin attenuates liver injury caused by vinyl chloride metabolite chloroethanol and lipopolysaccharide in mice.Toxicology and applied pharmacology · 2019Article
- Chronic + binge alcohol exposure promotes inflammation and alters airway mechanics in the lung.Alcohol (Fayetteville, N.Y.) · 2019Article
- Binge Alcohol Is More Injurious to Liver in Female than in Male Rats: Histopathological, Pharmacologic, and Epigenetic Profiles.The Journal of pharmacology and experimental therapeutics · 2019Article
- Vinyl chloride-induced interaction of nonalcoholic and toxicant-associated steatohepatitis: Protection by the ALDH2 activator Alda-1.Redox biology · 2019Article
- Chronic liver injury drives non-traditional intrahepatic fibrin(ogen) crosslinking via tissue transglutaminase.Journal of thrombosis and haemostasis : JTH · 2019Article
- TLR7-let-7 Signaling Contributes to Ethanol-Induced Hepatic Inflammatory Response in Mice and in Alcoholic Hepatitis.Alcoholism, clinical and experimental research · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledThe early stages of alcohol-induced liver injury involve chronic inflammation. Whereas mechanisms by which this effect is mediated are not completely understood, it is hypothesized that enhanced sensitivity to circulating lipopolysaccharide (LPS) contributes to this process. It has recently been shown that ethanol induces activation of plasminogen activator inhibitor-1 (PAI-1). PAI-1 causes fibrin accumulation in liver by inhibiting degradation of fibrin (fibrinolysis). LPS also enhances fibrin accumulation by activating the coagulation cascade. It was therefore hypothesized that ethanol will synergistically increase fibrin accumulation caused by LPS, enhancing liver damage. Accordingly, the effect of ethanol pretreatment on LPS-induced liver injury and fibrin deposition was determined in mice. Ethanol enhanced liver damage caused by LPS, as determined by plasma parameters and histological indices of inflammation and damage. This effect was concomitant with a significant increase in PAI-1 expression. Extracellular fibrin accumulation caused by LPS was also robustly increased by ethanol preexposure. Coadministration of the thrombin inhibitor hirudin or the MEK (mitogen-activated protein kinase) inhibitor U0126 significantly attenuated the enhanced liver damage caused by ethanol preexposure; this protection correlated with a significant blunting of the induction of PAI-1 caused by ethanol/LPS. Furthermore, thrombin/MEK inhibition prevented the synergistic effect of ethanol on the extracellular accumulation of fibrin caused by LPS. Similar protective effects on fibrin accumulation were observed in tumor necrosis factor receptor 1 (TNFR-1)(-/-) mice or in wild-type injected with PAI-1-inactivating antibody.
conclusionThese results suggest that enhanced LPS-induced liver injury caused by ethanol is mediated, at least in part, by fibrin accumulation in livers, mediated by an inhibition of fibrinolysis by PAI-1. These results also support the hypothesis that fibrin accumulation may play a critical role in the development of early alcohol-induced liver injury.
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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.