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2002 Fiscal Year Final Research Report Summary

An analysis and clinical application of hepatic sinusoidal cell function examined by signaling pathway.

Research Project

Project/Area Number 12470119
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

KOMATSU Yutaka  University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (90301100)

Co-Investigator(Kenkyū-buntansha) MATSUMURA Masayuki  University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
KANAI Fumihiko  University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (70334399)
SHIRATORI Yasushi  Okayama University, Professor, 大学院・医師学総合研究科, 教授 (70196624)
Project Period (FY) 2000 – 2002
KeywordsHepatic sinusoidal cells / Signal transduction / Stellate cell
Research Abstract

Aims of this study are to clarify an intercellular interaction and signaling pathway in hepatic sinusoidal cells using molecular biology technique, and to clarify control mechanism in the sinusoidal cells. In particular, we analyzed formation mechanism of angiogenesis of endothelial cells and intracellular signal transduction mechanism in liver fibrogenesis, sinusoidal endothelial cell proliferation in liver regeneration, and endothelial angiogenesis in cancer cell metastasis. Furthermore, to clarify an important factor concerned with control and a treatment of these liver disease state.
On the stellate cell which participated in liver fibrosis, we analyzed receptor, corepressor, and coactivator of RXR/RAR in collagen production and depression, also analized signal transduction in stellate cell by various cytokine stimuration and HBV, HCV and retinol. In analysis of a signal with cell proliferation mechanism of liver sinusoidal endothelial cells in liver regeneration, we analyzed VEGF receptor, Ras-MAPK signal pathway, p38, SAPK/JNK, JAK/STAT, PI3K-Akt, and JAK/STAT.
We used reporter plasmid pHTD2 which tied a CAT gene to promoter area of TGF-b1 in elucidation of control mechanism of liver disease by gene induction and elucidation of control mechanism in hepatic fibrogenesis. Furthermore, we elucidated that HBx protein and HCV core protein activated TGF-b1 promoter in dosage dependence. At the same time we clarified signal pathway in tissue inhibitor of metalloproteinase-1, -2 (TIMP). Furthermore, we anarized coherence with RAR, RXR which were receptor in retinoic acid, corepressor, coactivator and collagen gene expression.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Moriyama M et al.: "Relevance Network between Chemosensitivity and Transcriptome in Human Hepatoma Cells"Mol Cancer Ther. Feb,2(2). 199-205 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shiratori Y et al.: "Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus"Ann Intern Med. 18 138(4). 299-306 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hoshida Y et al.: "Identification of genes associated with sensitivity to 5-fluorouracil and cisplatin in hepatoma cells"J Gastroenterol. Nov;37 Suppl 14. 92-95 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Goyama S et al.: "Reverse seroconversion of hepatitis B virus after hematopoietic stem cell transplantation"Leuk Lymphoma. Nov;4,3(11). 2159-2163 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang Y et al.: "Interleukin-1 beta gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection"Hepatology. Jan;37(1). 65-71 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Owata M et al.: "Progression from chronic hepatitis to hepatocellular carcinoma ; Natural course and treatments"J Gastroenterol Hepatol. Dec;17 Suppl 3. S434-S436 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Moriyama M et al: "Relevance Network between chemo sensitivity and Transcriptome in Human Hepatoma Cells"Mol cancer Ther. 2. 199-205 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiratori Y et al: "Interferon therapy after tumor ablariou impcoves prognosis in patients with hepatomacellular carcinoma associated with hepatitis C virus"Ann Intern Med. 18 ; 138. 299-306 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hoshida Y. et al: "Indification of genes associated with sensitivity to 5-fluoroucacil and cisplatin in hepatoma cells"J. Gastroeuteral. 37 ; suppl 14. 92-95 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Goyama S et al: "Reverse secoconversion of hepatitis B virus after hepatopoietic stem cells transplantation"Leuk Lymphouna. 43 ; 11. 2159-2163 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wang Y et al: "Interleukin - 1 beta gene polymorphisms associated with hepatomacellular carcinoma in hepatitis C virus infection"Hepatology. 37 ; 1. 65-71 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Omata M et al: "progression from chronic hepatitis to hepatocellular carcinoma : Natural couice and treatments"J Gastroeuteiol Mepatol. 17 suppul 3. S434-S436 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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