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1990 Fiscal Year Final Research Report Summary

The Role of a New Hepatocyte Growth Factor in Liver Regeneration

Research Project

Project/Area Number 01571206
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionOkayama University

Principal Investigator

GOHDA Eiichi  Okayama University, Department of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20028814)

Project Period (FY) 1989 – 1990
KeywordsHepatocyte growth factor / Hepatocytes in primary culture / Hepatic injury / Liver regeneration / Carbon tetrachloride
Research Abstract

A mouse serum hepatocyte growth-stimulating activity markedly increased 24 h after carbon tetrachloride administration and then decreased. This time course of the activity was paralled with those of serum alanine and aspartate aminotransferses activities. hepatocyte growth-stimulating activity in liver extracts was low in untreated mice, but increased after carbon tetrachloride. The increase was detectable 12 h and marked 24 h after the hepatotoxin. It was maximal 48 h after the administration and then dropped gradually. Liver DNA synthesis began to rise and was highest 36 h and 48 h, respectively, after the hepatotoxin. Thus, the hepatocyte growth-stimulating activity in serum and liver increased prior to liver regeneration in carbon tetrachloride-treated mice. The elevated serum and liver activities may play an important role in promoting proliferation of liver cells in vivo subsequent to hepatic injury. Mouse hepatocyte growth factor (mHGF) was purified about 280,000-fold with 21% yield form the liver supernatant of mice treated with the hepatotoxin by ammonium sulfate fractionation followed by chromatography on Affi-Gel Blue, heparin-Sepharose and S-Sepharose. SDS-PolyacrylAmide Gel Electrophoresis (PAGE) of purified mHGF under nonreducing conditions showed a single band with a Molecular Weight (MW) of 76K, while two bands with MWs of 62K and 31K were detected after SDS-PAGE of reduced mHGF, showing that mHGF is a heterodimer. mHGF stimulated DNA synthesis of cultured hepatocytes as effectively as hHGF. The effect of mHGF was additive with the maximal effects of EGF and acidic FGF and synergistic with that of insulin, but not with the maximal effect of hHGF. Thus, the properties of mHGF are similar to those of hHGF. mHGF may be a hHGF-like factor with some structural differences from hHGF, because the activity of mHGF was not inhibited by rabbit anti-hHGF antiserum which neutralizes the hHGF activity.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] K.Miyazawa et al.: "Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor" Biochem.Biophys.Res.Commun.163. 967-973 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E.Gohda et al.: "Hepatotrophic growth factor in blood of mice treated with carbon tetrachloride" Life Sci.46. 1801-1808 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E.Gohda et al.: "Biological and immunological properties of human hepatocyte growth factor from plasma of patients with fulminant hepatic failure" Biochim.Biophys.Acta. 1053. 21-26 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E.Gohda et al.: "Hepatocyte growth factor in blood and liver of mice treated with hepatotoxins" Frontiers of Mucosal immunology(Proceedings of the sixth Iuternational Cougress of Mucosal Immunology). 101-104 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Tsubouchi et al.: "Human hepatocyte growth factor in blood of patieuts with fulminant hepatic failure I.clinical aspects" Dig.Dis.Sci.(1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E.Gohd et al.: "Human hepatocyte growth factor in blood of patieuts with fulminant hepatic Facilure Basic aspects" Dig.Dis.Sci.(1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Miyazawa et al.: "Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor" Bio chem. Bio phys. Res. Commun.163. 967-973 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E. Gohda et al.: "Hepatotrophic growth factor in blood of mice treated with carbon tetrachloride" Life Sci.46. 1801-1808 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E. Gohda et al.: "Biological and immunological properties of human hepatocyte growth factor from plasma of patients with fulminant hepatic failure" Biochim. Biophys. Acta. 1053. 21-26 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E. Gohda et al.: "Hepatocyte growth factor in blood and liver of mice treated with hepatotoxins" Frontiers of Mucosal Immunology (Proceedings of the Sixth International Mucosal Immunology). (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Tsubouchi et al.: "Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. I. Clinical aspects" Dig. Dis. Sci.(1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E. Gohda et al.: "Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. Basic aspects" Dig. Dis. Sci.(1991)

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

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Published: 1993-08-12  

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