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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-9-22
pubmed:abstractText
Pleiotrophin (PTN) is a hepatocyte growth factor and considered to play roles in liver fibrogenesis and hepatocarcinogenesis. In this study we examined the mechanism of the action of PTN in these pathological processes. First, we confirmed that hepatic stellate cells (HSCs) and Kupffer cells, and also later hepatocytes in hyperplastic nodules increased PTN mRNA expressions during carbon tetrachloride-induced liver fibrosis. Then, the relationship between PTN and transforming growth factor beta1 (TGFbeta1), a known potent pro-fibrogenetic cytokine, in carcinogenesis was investigated using hepatoma cell lines. Huh-7 human hepatoma cells weakly expressed PTN, but HepG2 human hepatoma cells and FaO rat hepatoma cells did not. Recombinant (r) TGFbeta1 induced the cultured Huh-7 cells to undergo apoptosis, which was inhibited by rPTN. Huh-7 cells became resistant to TGFbeta1-, but not mitomycin C-induced apoptosis when transfected with PTN gene, indicating the specificity of the PTN anti-apoptotic activity. Poly ADP ribose polymerase, procaspase-8 and procaspase-3 were not cleaved in the TGFbeta1-reluctant cells. The TGFbeta1-induced caspase-3 activation was also suppressed in Huh-7 and FaO cells both transduced with PTN gene-bearing adenoviruses. In summary, PTN was expressed in HSCs, Kupffer cells, and hepatocytes in fibrotic liver. We propose that PTN specifically antagonizes the TGFbeta1 activity during liver fibrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-2744
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
784-96
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Pleiotrophin inhibits transforming growth factor beta1-induced apoptosis in hepatoma cell lines.
pubmed:affiliation
Biochemistry and Molecular biology, School of Medicine, Ajou University, Suwon, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't