Linked Life Data

21356363

Source:http://linkedlifedata.com/resource/pubmed/id/21356363

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-1
pubmed:abstractText
Chronic cholestatic liver injury induced by cholestasis in rodents is associated with hepatic fibrin deposition, and we found evidence of fibrin deposition in livers of patients with cholestasis. Key components of the fibrinolytic pathway modulate cholestatic liver injury by regulating activation of hepatocyte growth factor. However, the exact role of hepatic fibrin deposition in chronic cholestasis is not known. We tested the hypothesis that fibrinogen (Fbg) deficiency worsens liver injury induced by cholestasis. Fbg-deficient mice (Fbg?(-/-) mice) and heterozygous control mice (Fbg?(+/-) mice) were fed either the control diet or a diet containing 0.025% ?-naphthylisothiocyanate (ANIT), which selectively injures bile duct epithelial cells in the liver, for 2 weeks. Hepatic fibrin and collagen deposits were evident in livers of heterozygous control mice fed the ANIT diet. Complete Fbg deficiency was associated with elevated serum bile acids, periportal necrosis, and increased serum alanine aminotransferase activity in mice fed the ANIT diet. Fbg deficiency was associated with enhanced hepatic expression of the transcription factor early growth response-1 (Egr-1) and enhanced induction of genes encoding the Egr-1-regulated proinflammatory chemokines monocyte chemotactic protein-1, KC growth-regulated protein, and macrophage inflammatory protein-2. Interestingly, peribiliary collagen deposition was not evident near necrotic areas in Fbg-deficient mice. The results suggest that in this model of chronic cholestasis, fibrin constrains the release of bile constituents from injured intrahepatic bile ducts, thereby limiting the progression of hepatic inflammation and hepatocellular injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1525-2191
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1117-25
pubmed:meshHeading
pubmed-meshheading:21356363-1-Naphthylisothiocyanate, pubmed-meshheading:21356363-Afibrinogenemia, pubmed-meshheading:21356363-Aged, pubmed-meshheading:21356363-Animals, pubmed-meshheading:21356363-Bile Ducts, pubmed-meshheading:21356363-Cholestasis, pubmed-meshheading:21356363-Chronic Disease, pubmed-meshheading:21356363-Collagen, pubmed-meshheading:21356363-Diet, pubmed-meshheading:21356363-Disease Models, Animal, pubmed-meshheading:21356363-Early Growth Response Protein 1, pubmed-meshheading:21356363-Feeding Behavior, pubmed-meshheading:21356363-Female, pubmed-meshheading:21356363-Fibrin, pubmed-meshheading:21356363-Fibrinogen, pubmed-meshheading:21356363-Gene Expression Regulation, pubmed-meshheading:21356363-Humans, pubmed-meshheading:21356363-Hyperplasia, pubmed-meshheading:21356363-Inflammation, pubmed-meshheading:21356363-Liver, pubmed-meshheading:21356363-Liver Cirrhosis, pubmed-meshheading:21356363-Male, pubmed-meshheading:21356363-Mice, pubmed-meshheading:21356363-Middle Aged, pubmed-meshheading:21356363-Neutrophils, pubmed-meshheading:21356363-Xenobiotics
pubmed:year
2011
pubmed:articleTitle
Fibrinogen deficiency increases liver injury and early growth response-1 (Egr-1) expression in a model of chronic xenobiotic-induced cholestasis.
pubmed:affiliation
Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA. jluyendyk@kumc.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural