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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1996-8-29
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pubmed:abstractText |
During liver fibrogenesis, Ito cells are regarded as the principal matrix synthesizing cells and transforming growth factor beta 1 (TGF-beta 1) appears to be the main fibrogenic mediator. This study analyzed the effects of TGF-beta 1 on Ito cell activation, proliferation, and on the expression of a set of matrix proteins, antiproteases, and TGF-beta receptors both in "early cultured" and "culture-activated" Ito cells. Rat liver Ito cells at day 2 of primary culture ("early cultured" cells) were mainly smooth muscle alpha actin (SMA)-negative, whereas cells at day 6 were judged as "activated" cells (SMA-positive). Following 24-hour exposure to 1 ng/mL TGF-beta 1, total protein synthesis, cell proliferation, and expression of the "activation" marker SMA were not significantly changed. In addition to previously described stimulatory effects on collagen types I and III, fibronectin, undulin, and proteoglycan-gene expression, TGF-beta also dose-dependently increased synthesis and secretion of tenascin, laminin, entactin, collagen type IV, and alpha 2-macroglobulin, but decreased C1-esterase inhibitor production by Ito cells, as revealed by immunoprecipitation of endogenously labeled proteins and by Northern blot analysis. The stimulatory effect of TGF-beta was evident both in "early cultured" as well as "culture-activated" Ito cells. By reverse-transcription polymerase chain reaction (RT-PCR) analysis, TGF-beta type II, III, and TGF-beta/activin type I receptors were present in Ito cells, and their expression pattern was not changed upon TGF-beta exposure. Northern blot analysis demonstrated that type I TGF-beta/activin receptor was induced during in vitro activation and that TGF-beta exposure resulted in a slight increase of type I and III receptor messenger RNAs. In summary, the data illustrate that TGF-beta is an important fibrogenic mediator acting both on "early cultured" as well as "culture-activated" Ito cells, rather than a mitogenic or morphogenic mediator. The differential regulation of TGF-beta/activin receptors during in vitro activation and their up-regulation by TGF-beta 1 might represent a mechanism by which the receptor complex regulates TGF-beta signalling in Ito cells.
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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 |
0270-9139
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
352-60
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8690404-Adipocytes,
pubmed-meshheading:8690404-Animals,
pubmed-meshheading:8690404-Base Sequence,
pubmed-meshheading:8690404-Cell Division,
pubmed-meshheading:8690404-Cells, Cultured,
pubmed-meshheading:8690404-Extracellular Matrix Proteins,
pubmed-meshheading:8690404-Gene Expression Regulation,
pubmed-meshheading:8690404-Liver,
pubmed-meshheading:8690404-Molecular Sequence Data,
pubmed-meshheading:8690404-Rabbits,
pubmed-meshheading:8690404-Rats,
pubmed-meshheading:8690404-Rats, Wistar,
pubmed-meshheading:8690404-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:8690404-Transforming Growth Factor beta
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pubmed:year |
1996
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pubmed:articleTitle |
Transforming growth factor beta 1-regulated gene expression of Ito cells.
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pubmed:affiliation |
Department of Internal Medicine, University of Göttingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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