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Studies on competence factors in hepatocyte proliferation

Research Project

Project/Area Number 02670296
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionUniversity of Tokyo

Principal Investigator

HASHIMOTO Naoaki  University of Tokyo, Faculty of Medicine, 医学部(付属病院), 助手 (00167579)

Co-Investigator(Kenkyū-buntansha) WATANABE Tsuyoshi  University of Tokyo, Faculty of Medicine, 医学部(付属病院), 助手 (80158641)
IKEDA Yusei  University of Tokyo, Faculty of Medicine, 医学部(付属病院), 助手 (80133073)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordshepatocyte Proliferation / competence factor / Prostaglandin / receptor / signal transduction / primary culture of hepatocyte / sinusoidal cells / liver regeneration / コンピテンス因子 / プロスタグラレディン / 類洞細胞
Research Abstract

The studies on hepatocyte proliferation has been made great advance in recent years using primary cultures of hepatocytes. Several growth factors were anticipated that they played important roles in liver regeneration through their proliferative activities on hepatocytes., However, little is known about the "trigger" factor (s) of liver regeneration. It was reported that two kinds of growth factors acted sequentially in fibroblast proliferation : competence f-actor and progression factor. Although physiological coinpe-tence factor of hepatocytes has never been reported, it would probably be a trigger factor of liver regeneration because it can act on quiescent cells and can make them sensitive to progression factors.
In the present studies, we found that the density of prostaglandin (PG) E_2 receptors on the rat hepa-Locytes in primary culture was decreased when cells were prepared from the rats received partial hepatectomy. We concluded that this decrease was the down regulation of PGE_2 receptors reflecting the direct exposure of the hepatocytes to PGE_2 in vivo after the surgery.
In addition, we revealed that PGs had proliferative activities on hepatocyte in serum-free primary culture by enhancing their sensitivity to insulin plus epidermal growth factor. This activity was most prominent in PGE_2, and the action was mediated through stereo-specific PGE_2 receptor and pertusis toxin sensitive G-protein. PGF_2 alpha in higher concentration could act by cross-reacting to PGE_2 receptor. PG actions were, at least in part, mediated by the increase in the intracellular Ca^<2+> concentration. PGE_2 might be derived from sinusoldal endotherial cells, because cultured cells secreated PGE_2.
In conclusion, PGE_2 was suggested to be a competence factor in hepatocyte proliferation, and to act as a trigger factor for liver regeneration.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Hashimoto N,Watanabe T,Ikeda Y,Toda G,Yamada H,Yoshikawa,Y,Mitsui H and Kurokawa K.: "Down-regulation of Prostaglandin Ei receftors in regenerating rat liver and its physiologicol significance." Biochem.Biophys.Res Commun. 176. 226-232 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mitsui H,Iwanori M,Hashimoto N,Yamada H,Ikeda Y,Toda G,Kurokawa K and Nagai Y.: "The B Subunit of Cholera Toxin enhances DNA synthesis in rat hepatocytes induced by insnlin and efidermal growth factor." Biochem.Biophys.Res.Commun. 174. 372-378 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 橋本 直明,渡辺 毅,戸田 剛太郎,池田 有成,山田 春木,吉川 雄二,光井 洋,丸山 稔之: "ラット無血清初代培養肝細胞の増殖に対するプロスタグランディンの効果" 肝臓. 31. 1244-1245 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 橋本 直明: "肝障害とプロスタグランディンー基礎から臨床応用へ向けてー" Biomedica. 6. 163-169 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 橋本 直明,池田 有成: "ラット部分肝切除後再生肝におけるPGE_2受容体の変動ー初代培養肝細胞による検討(パネルディスカッション,消化器とプロスタグランディン)" 日本消化器病学会雑誌. 87. 454 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N,Watanabe T,Toda G,Ikeda Y,Yamada H,Yoshikawa Y,Mitsui H,and Kurokawa K.: "Effects of prostaglandin on proliferation of hepatocytes in primary culture" Hepatology. 12. 409 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N, Watanabe T, Ikeda Y, Toda G, Yamada H, Yoshikawa Y, Mitsui H and Kurokawa K.: "Down-regulation of prostaglandin e_2 receptors in regenerating rat liver and its physiological significance." Biochem biophys Rec commun. 176. 226-232 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mitsui H, Iwamori M, Hashimoto N, Yamada H, Ikeda Y, Toda G, Kurokawa K and Nagai Y.: "The B subunit of cholera toxin enhances DNA synthesis in rat hepatocytes induced by insulin and epidermal growth factor." Biochem Biophys Rec commun. 174. 372-378 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N, Watanabe T, Toda G, Ikeda Y, Yamada H, Yoshikawa Y, Mitsui H and Kurokawa K.: "Proliferative effects of prostaglandins on DNA synthesis in primary rat hepatocyte cultures."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N, Watanabe T, Toda G, Ikeda Y, Yamada H, Yoshikawa Y, Mitsui H, Maruyama T and Kurokawa K.: "Effects of prostaglandins on growth of hepatocytes in serum-free primary culture." Acta Hepatologica Jpn. 31. 1244-1245 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N.: "Liver disorders and prostaglandins. ---- Basic research and clinical problems." BIOmedica. 6. 163-168 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N, Watanabe T, Ikeda Y, Toda G, Yamada H, Yoshikawa Y, Maekawa H, Mitsui H, and Oka H.: "Properties of prostaglandin E_2 receptor in primary Hepatocytes cultures from regenerating rat liver after partial hepatectomy." Proceedings of The Japan Society of Clinical Biochemistry and Metabolism (XXVI). 426-427 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N and Ikeda Y.: "Properties of prostagland in E_2 receptor in regenerating rat liver after partial hepatectomy. ----Studies using primary cultures." Jap J Gastroenterol. 87 (Suppl). 454 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N, Watanabe T, Toda G, Ikeda Y, Yamada H, Yoshikawa Y, Mitsui H and Kurokawa K.: "Effects of prostaglandins on proliferation of hepatocytes in primary culture." hepatology. 12. 409 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hasimoto N, Toda G, Ikeda Y, Watanabe T, yamada H, Mitsui H, Yoshikawa Y, Han KK, Kashiwagi M and Kurokawa K.: "Down-regulation of prostaglandin E_2 receptors in regenerating rat liver and its physiological significance." Acta Hepatologica Jpn. 32 (Suppl). 127 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto N,Watanabe T,Ikeda Y,Toda G,Yamada H,Yoshikawa Y,Mitsui H and Kurokawa K: "Downーregulation of prostaglandin E_2 receptors in regenerating rat liver and its physiolgical significance" Biochem,Biophys,Res,Commun,. 176. 226-232 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hashimoto N,Watanabe T,Toda G,Ikeda Y,Yamada H,Yoshikawa Y,Mitsui H,and Kurokawa: "Prolifera effects of proscoglanders on DNA synthens in primary rat hepatoyte"

    • Related Report
      1991 Annual Research Report
  • [Publications] 橋本 直明,戸田 剛太郎,池田 有成,渡辺 毅,山田 春木,光井 洋,吉川 雄二,満 浩憲,柏木 万寿男,黒川 清: "ラット再生肝細胞のプロスタグランディン(PG)E_2受容体のdown regulationとその意義" 肝臓. 32. (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Mitsui,H.,Iwamori,M.,Hashimoto,N.,Yamada,H.,Ikeda,Y.,Toda,G.,et al: "The B subunit of cholera toxin enhances DNA synthesis in rat hepatocytes induced by insulin and epidermal growth factor." Biochem.Biophys.Res.Commura.174. 372-378 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 橋本 直明、渡辺 毅、戸田 剛太郎、池田 有成、山田 春木、吉川 雄二他: "ラット無血清初代培養肝細胞の増殖に対するプロスタグランディンの効果" 肝臓. 10. 1244-1245 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 橋本 直明: "肝障害とプロスタグランディンー基礎から臨床応用へむけてー" Biomedica. 6. 163-169 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 橋本 直明、池田 有成: "ラット部分肝切除後再生肝におけるPGE_2受容体の変動ー初代培養肝細胞による検討(パネルディスカッション,消化器疾患とプロスタグランディン)" 日本消化器病学会雑誌. 87. 454 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hashimoto N,Watanabe T,Toda G,Ikeda Y,Yamada H,Yoshikawa Y,Mitsui H,et al: "Effects of prostageandins on proliferation of hepatocytes in primary culture." Hepatology. 12. 409 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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