{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:42:20Z","timestamp":1784763740221,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2008,3,31]],"date-time":"2008-03-31T00:00:00Z","timestamp":1206921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010induced liver fibrosis. Then, the relationship between PTN and transforming growth factor \u03b21 (TGF\u03b21), a known potent pro\u2010fibrogenetic cytokine, in carcinogenesis was investigated using hepatoma cell lines. Huh\u20107 human hepatoma cells weakly expressed PTN, but HepG2 human hepatoma cells and FaO rat hepatoma cells did not. Recombinant (r) TGF\u03b21 induced the cultured Huh\u20107 cells to undergo apoptosis, which was inhibited by rPTN. Huh\u20107 cells became resistant to TGF\u03b21\u2010, but not mitomycin C\u2010induced apoptosis when transfected with PTN gene, indicating the specificity of the PTN anti\u2010apoptotic activity. Poly ADP ribose polymerase, procaspase\u20108 and procaspase\u20103 were not cleaved in the TGF\u03b21\u2010reluctant cells. The TGF\u03b21\u2010induced caspase\u20103 activation was also suppressed in Huh\u20107 and FaO cells both transduced with PTN gene\u2010bearing adenoviruses. In summary, PTN was expressed in HSCs, Kupffer cells, and hepatocytes in fibrotic liver. We propose that PTN specifically antagonizes the TGF\u03b21 activity during liver fibrosis. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20438","type":"journal-article","created":{"date-parts":[[2008,3,31]],"date-time":"2008-03-31T14:58:46Z","timestamp":1206975526000},"page":"784-796","source":"Crossref","is-referenced-by-count":16,"title":["Pleiotrophin inhibits transforming growth factor \u03b21\u2010induced apoptosis in hepatoma cell lines"],"prefix":"10.1002","volume":"47","author":[{"given":"Tae Jun","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Ra","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chise","family":"Tateno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong 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