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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0002198,
umls-concept:C0017262,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0178539,
umls-concept:C0185117,
umls-concept:C0239946,
umls-concept:C0331858,
umls-concept:C1704640,
umls-concept:C1706515,
umls-concept:C1879547,
umls-concept:C2340138,
umls-concept:C2348519,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
1998-12-16
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pubmed:abstractText |
1. Hepatic stellate cells are key mediators of hepatic fibrosis. We have studied hepatic stellate cell expression of the collagenase and general protease inhibitor alpha2-macroglobulin after activation in tissue culture and in response to certain cytokines. 2. Hepatic stellate cells isolated by Pronase-collagenase digestion were activated by culture on uncoated plastic. By Northern analysis hepatic stellate cells undergoing activation (5 days) expressed alpha2-macroglobulin mRNA and alpha2-macroglobulin could be immunolocalized to hepatic stellate cells from 5 to 15 days of culture. 3. By ELISA of cell culture supernatants hepatic stellate cell secretion of alpha2-macroglobulin was found to increase from 2. 78+/-1.13 ng x ml-1 x microgram-1 DNA per 24 h at 5 days of culture (n=8) to 13.55+/-4.64 ng x ml-1 x microgram-1 DNA per 24 h at 15 days of culture (n=7). Stimulation of hepatic stellate cells with interleukin-6 at 5 days caused a significant increase in alpha2-macroglobulin expression as did exposure to Kupffer-cell conditioned medium. However, exposure of hepatic stellate cells to interleukin-1, transforming growth factor-beta1 and tumour necrosis factor-alpha had no significant effect. 4. During profibrotic liver injury plasma alpha2-macroglobulin levels were found to increase to between 850% and 250% of the control value (100%) after bile duct ligation (72 h to 13 days respectively), and to 1166% and 1106% of the control value during progressive CCl4-induced fibrosis (24 h to 4 weeks respectively). 5. These data suggest that hepatic stellate cells are a potential source of the potent protease inhibitor alpha2-macroglobulin, expression of which may inhibit matrix remodelling during progressive fibrosis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0143-5221
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
179-86
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:9680500-Animals,
pubmed-meshheading:9680500-Biological Markers,
pubmed-meshheading:9680500-Blotting, Northern,
pubmed-meshheading:9680500-Cell Separation,
pubmed-meshheading:9680500-Cells, Cultured,
pubmed-meshheading:9680500-Disease Models, Animal,
pubmed-meshheading:9680500-Interleukin-6,
pubmed-meshheading:9680500-Liver,
pubmed-meshheading:9680500-Liver Cirrhosis,
pubmed-meshheading:9680500-RNA, Messenger,
pubmed-meshheading:9680500-Rats,
pubmed-meshheading:9680500-Stimulation, Chemical,
pubmed-meshheading:9680500-alpha-Macroglobulins
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pubmed:year |
1998
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pubmed:articleTitle |
Rat hepatic stellate cell expression of alpha2-macroglobulin is a feature of cellular activation: implications for matrix remodelling in hepatic fibrosis.
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pubmed:affiliation |
University Medicine, University of Southampton, Southampton SO16 6YD, Hampshire, U.K.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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