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2004 Fiscal Year Final Research Report Summary

Identification and characterization of the phenotype of hepatic stem cells in various liver diseases, its application to frontier medicine

Research Project

Project/Area Number 14370068
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKobe University

Principal Investigator

HAYASHI Yoshitake  Kobe University, School of Medicine, Professor, 医学部, 教授 (50189669)

Co-Investigator(Kenkyū-buntansha) GU Eisei  Kobe University, School of Medicine, Professor, 医学部, 教授 (40195615)
SEO Yasushi  Kobe University, Grad Sch. Medicine, Assistant, 大学院・医学系研究科, 助手 (90362772)
KANOMATA Naoki  Kobe University Hospital, School of Medicine, Assistant, 医学部附属病院, 助手 (60263373)
Project Period (FY) 2002 – 2004
KeywordsHNF / Oval cell / Hepatocellular carcinoma / Regeneration / Stem cell / Hepatic stemcell / Fatty change of liver / Nonalcoholic steatohepatitis (NASH)
Research Abstract

During regeneration of liver tissue, oval cells which don't die by apoptosis, induces apoptosis in surrounding hepatocytes. Administration of 2-acetylaminofluorene (2-AAF) followed by partial hepatectomy causes proliferation of oval cell in rats. Caspase-3, Fas, Fas-L and Bax expressed in hepatocytes, but not in oval cells. This may be the molecular mechanism that the oval cells, without any damage in itself, induce apoptosis of surrounding hepatocytes (J Gastroenterol Hepatol19(8) :866-872, 2004). Diethylnitrosamine (DEN) was given to same animal model before administration of 2-AAF to induce hepatocellular carcinom to estimate the efficacy of INF-alpha for prevention of HCC (Carcinogenesis 25(3) :389-397, 2004). Alteration of iver-enriched nuclear protein and signal transduction related to fat-droplets in hepatocytes is also involving the differentiation of liver and pancreatic cell, and onset of diabetes. The report that the activation of protein kinase C is related to fatty changes of liver and insulin-sensitivity (J Clin Investigation 112:935-944, 2003). The protein p27(Kip1) regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). We show that p27(Kip1) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db). p27(Kip1) contributes to beta-cell failure during the development of type 2 diabetes in Irs2(-/-) and Lepr(-/-) mice and represents a potential new target for the treatment of this condition. (Nature Medicine ll(2):175- 182, 2005).

  • Research Products

    (17 results)

All 2005 2004 2003

All Journal Article (17 results)

  • [Journal Article] Accumulation of hRad9 protein in the nuclei of nonsmall cell lung carcinoma cells2005

    • Author(s)
      Maniwa Y
    • Journal Title

      Cancer 103(1)

      Pages: 126-132

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice2005

    • Author(s)
      Uchida T
    • Journal Title

      Nature Medicine 11(2)

      Pages: 175-182

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prediction of efficacy of interferon treatment of chronic hepatitis C and occurrence of HCC after interferon treatment by a new classification.2005

    • Author(s)
      Kim KI
    • Journal Title

      Intervirology 48(1)

      Pages: 52-58

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice2005

    • Author(s)
      Tohru, Uchida
    • Journal Title

      Nature Medicine 11-2

      Pages: 175-182

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prediction of efficacy of interferon treatment of chronic hepatitis C and occurrence of HCC after interferon treatment by a new classification2005

    • Author(s)
      Ke Ih, Kim
    • Journal Title

      Intervirology 48-1

      Pages: 52-58

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat2004

    • Author(s)
      Nakaji M
    • Journal Title

      Carcinogenesis 25(3)

      Pages: 389-397

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Response to interferon-alpha in chronic hepatitis B with and without Precore mutant strain detected by mutation site-specific assay2004

    • Author(s)
      Seo Y
    • Journal Title

      J Clin Gastroenterol 38(5)

      Pages: 460-464

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Apoptotic pathway related to oval cell proliferation2004

    • Author(s)
      Yano Y
    • Journal Title

      J Gastroenterol Hepatol 19(8)

      Pages: 866-872

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat2004

    • Author(s)
      Miyuki, Nakaji
    • Journal Title

      Carcinogenesis 25-3

      Pages: 389-397

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression and localization of ecto-nucleotide pyrophosphatase /phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130 (RB13-6)) in inflammatory and neoplastic bile duct diseases2004

    • Author(s)
      Yoshihiko, Yano
    • Journal Title

      Cancer Lett 207-2

      Pages: 139-147

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Response to interferon-alpha in chronic Hepatitis B with and without Precore mutant strain detected by mutation site-specific assay2004

    • Author(s)
      Yasushi, Seo
    • Journal Title

      J Clin Gastroenterol 38-5

      Pages: 460-464

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Apoptotic pathway related to oval cell proliferation2004

    • Author(s)
      Yoshihiko, Yano
    • Journal Title

      J Gastroenterol Hepatol 19-8

      Pages: 866-872

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Accumulation of hRad9 protein in The nuclei of nonsmall cell lung carcinoma cells2004

    • Author(s)
      Yoshimasa, Maniwa
    • Journal Title

      Cancer 103-1

      Pages: 126-132

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Down-regulation of stomach cancer associated protein tyrosine phospatase-1 (SAP-1) in advanced human hepatocellular carcinoma2003

    • Author(s)
      Nagano H
    • Journal Title

      Oncogene 22(23)

      Pages: 4656-4663

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Protein kinase Cl in liver insulin-induced SREBP-1c expression and determineboth hapatic lipid content and overall insulin Sensitivity.2003

    • Author(s)
      Matsumoto M
    • Journal Title

      J Clin Investigation 112(6)

      Pages: 935-944

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Down-regulation of stomach cancer associated protein tyrosine phosphatase-1 (SAP-1) in advanced human hepatocellular carcinoma2003

    • Author(s)
      Hidenobu, Nagano
    • Journal Title

      Oncogene 22-30

      Pages: 4656-4663

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Protein kinase Cl in liver mediates insulin-induced SREBP-1c expression and determine both hepatic lipid content and overall insulin sensitivity2003

    • Author(s)
      Michihiro, Matsumoto
    • Journal Title

      J Clin Investigation 112-6

      Pages: 935-944

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

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Published: 2006-07-11  

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