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http://purl.uniprot.org/citations/25353084http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25353084http://www.w3.org/2000/01/rdf-schema#comment"

Background

The 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.

Objectives

To 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.

Methods

Biliary 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.

Results

Elevated 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.

Conclusions

Collectively, 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."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.org/dc/terms/identifier"doi:10.1111/jth.12770"xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Joshi N."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Williams K.J."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Flick M.J."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"O'Brien K.M."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Luyendyk J.P."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Copple B.L."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Kopec A.K."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Towery K.L."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/author"Cline-Fedewa H."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/name"J Thromb Haemost"xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/pages"57-71"xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/title"Coagulation-driven platelet activation reduces cholestatic liver injury and fibrosis in mice."xsd:string
http://purl.uniprot.org/citations/25353084http://purl.uniprot.org/core/volume"13"xsd:string
http://purl.uniprot.org/citations/25353084http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25353084
http://purl.uniprot.org/citations/25353084http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25353084
http://purl.uniprot.org/uniprot/#_Q0VDX1-mappedCitation-25353084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25353084
http://purl.uniprot.org/uniprot/#_O88634-mappedCitation-25353084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25353084
http://purl.uniprot.org/uniprot/#_Q3UEM7-mappedCitation-25353084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25353084
http://purl.uniprot.org/uniprot/#_Q3UER8-mappedCitation-25353084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25353084
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http://purl.uniprot.org/uniprot/O88634http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/25353084
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