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Pleiotrophin inhibits transforming growth factor β1‐induced apoptosis in hepatoma cell lines
Author(s) -
Park Tae Jun,
Jeong Bo Ra,
Tateno Chise,
Kim Hong Seok,
Ogawa Tomohiro,
Lim In Kyoung,
Yoshizato Katsutoshi
Publication year - 2008
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20438
Subject(s) - pleiotrophin , biology , transfection , apoptosis , hepatic stellate cell , hepatocyte , microbiology and biotechnology , cell culture , paracrine signalling , transforming growth factor , cytokine , carcinogenesis , cancer research , cell growth , growth factor , gene , immunology , endocrinology , in vitro , receptor , biochemistry , genetics
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 β1 (TGFβ1), 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) TGFβ1 induced the cultured Huh‐7 cells to undergo apoptosis, which was inhibited by rPTN. Huh‐7 cells became resistant to TGFβ1‐, 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 TGFβ1‐reluctant cells. The TGFβ1‐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 TGFβ1 activity during liver fibrosis. © 2008 Wiley‐Liss, Inc.