32 276

Cited 0 times in

Pleiotrophin inhibits transforming growth factor beta1-induced apoptosis in hepatoma cell lines.

Park, TJ; Jeong, BR; Tateno, C; Kim, HS; Ogawa, T; Lim, IK; Yoshizato, K
Molecular carcinogenesis, 47(10):784-796, 2008
Journal Title
Molecular carcinogenesis
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.
MeSH terms
AnimalsApoptosis/physiology*Carcinoma, Hepatocellular/pathology*Carrier Proteins/physiology*Cell Line, TumorCytokines/physiology*ImmunohistochemistryLiver Neoplasms/pathology*MaleRatsRats, Inbred F344Reverse Transcriptase Polymerase Chain ReactionTransforming Growth Factor beta1/physiology*
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
박, 태준김, 홍석임, 인경
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.