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REGULATION OF HEPATOCYTE GROWTH

Research Project

Project/Area Number 10470136
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionYAMAGUCHI UNIVERSITY

Principal Investigator

OKITA Kiwamu  YAMAGUCHI UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (70107738)

Co-Investigator(Kenkyū-buntansha) KUBO Yoshitugu  YAMAGUCHI UNIVERSITY HOSPITAL, Clinical Fellow, 医学部・附属病院, 医員(臨床)
MASUHARA Masaaki  YAMAGUCHI UNIVERSITY, SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (80294627)
SAKAIDA Isao  YAMAGUCHI UNIVERSITY HOSPITAL, RESEARCH ASSOCIATE, 医学部・附属病院, 助手 (80263763)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsHGF / TGF-β / EXTRACELLULAR MATRIX / 細胞外マトリックス / 肝細胞 / 癌細胞 / 前癌性病変 / シグナル伝達 / TGF-β1 / 線維化
Research Abstract

The reguration of hepatocyte regeneration has been thought the balane betwen inhibitory cytokines i. e. TGF-β and accelerating cytokines i. e. HGF.It has been reported that main TGF-b producing cell is the stellate cell which palys an important role of fibrosis in the liver. Under chronic inflamatory condition, either regenerated hepatocyte or extarcellular matrix, which stellate cell mainly produces, will replace the necrotic tissue. Also NK cell may be involved in the regulation of hepatocyte regeneration. The results of this study are followings ;
(1) Pig serum treatment twice a week induced hepatic fibrosis with increased TGF-β expression and 70% hepatectomy of this TGF-β induced liver showed retarded regeneration compared with normal liver.
(2) Choline deficient diet induced liver cirrhosis with preneoplastic lesions and hepatocellular carcinoma with incerased TGF-b expression by activated stellate cell and preneoplastic lesions are surrounded with activated stellate cell, producing TGF-β The extent of growth (regeneration) rate of these hepatocytes in the preneoplastic lesions is more than that of normal hepatocytes. Thus preneoplastic lesions are already escaped from the regulation of TGF-β.
(3) NK cell may attack inmature regenerated hepatocytes and retard hepatic regeneration.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Okita K. et al.: "Correlation between stellate cell activation and serum fibrosis markers in choline-deficient L-amino acid-defined diet-induced rat liver fibrosis."Dig Dis Sci.. 45. 1935-1943 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita K. et al.: "Preventive effect of FK 506(tacrolimus hydrate)on experimentally induced acute liver injury in rats."Dig Dis Sci.. 45. 1996-2001 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita K. et al.: "GB virus C/hepatitis Gviremia and antibody response to the E2 protein of hepatitis Gvirus in hemodialysis patients."J Clin Gastroenterol.. 30. 425-428 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita K. et al.: "Loss of inhibitory growth regulation by TGF-beta1 in preneoplastic lesions in rat liver."Dig Dis Sci.. 45. 325-333 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita K. et al: "Augmenter of liver regeneration (ALR) may promote liver regeneration byreducing natural killer(kk)cell activity in human liver disease"J Gastroenterol.. 35. 112-119 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita K.et al.: "Correlation between stellate cell activation and serum fibrosis markers in choline-deficient L-amine acid-defined diet-induced rat liver fibrosis."Dig Dis Sci.. 45. 1935-43 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita K.et al.: "Preventive effect of FK506 (tacrolimus hydrate) on experimentally induced acute liver injury in rats."Dig Dis Sci.. 45. 1996-2001 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita k. et al.: "GB virus C/hepatitis Gviremia and antibody response to the E2 protein of hepatitis G virus in hemodialysis patients."J Clin Gastroenterol.. 30. 425-28 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita et al.: "Loss of inhibitory growth regulation by TGF-beta1 in preneoplastic lesions in rat liver."Dig Dis Sci.. 45. 325-33 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita et al.: "Augmenter of liver regeneration (ALR) may promote iver regeneration by reducing natural killer (NK) cell activity in human liver diseases."J Gastroenterol.. 35. 112-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okita K. et al.: "Correlation between stellate cell activation and serum fibrosis markers in choline-deficient L-amino acid-defined diet-induced rat liver fibrosis."Dig Dis Sci.. 45. 1935-1943 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okita K. et al.: "Preventive effect of FK506 (tacrolimus hydrate) on experimentally induced acute liver injury in rats."Dig Dis Sci.. 45. 1996-2001 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okita K. et al.: "GB virus C/hepatitis G viremia and antibody response to the E2 protein of hepatitis G virus in hemodialysis patients."J Clin Gastroenterol.. 30. 425-428 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okita K. et al.: "Loss of inhibitory growth regulation by TGF-beta1 in preneoplastic lesions in rat liver."Dig Dis Sci.. 45. 325-333 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okita K. et al.: "Augmenter of liver regeneration (ALR) may promote liver regeneration by reducing natural killer (NK) cell activity in human liver diseases"J Gastroenterol.. 35. 112-119 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okita K et al.: "Genetic aberrations detected by comparative genomic hybridization in hepatocellular carcinomas: their relationship to clinicopathological features."Hepatology. 29. 1858-1862 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okita K et al.: "Genetic aberrations detected by comparative genomic hybridization in biliary tract cancers."Oncology. 57. 42-49 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okita K et al.: "Enhanced interstitial collagenase(Matrix metalloproteinase-13) production of kupffer cell by gadolinium chloride prevents pig serum-induced rat liver fibrosis."Biochem Biophys Res Commun. 267. 290 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okita K et al.: "Detection of K-ras and p53 gene mutations in pancreatic juice for the diagnosis of intraductal papillary mucinous tumors."Pancreas. 18. 294-299 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okita K et al.: "Iron chelator deferoxamine reduces preneoplastic lesions in liver induced by choline-deficient L-amino acid-defined diet in rats."Dig Dis Sci. 44. 560-569 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okita K et al.: "Prolyl 4-hydroxylase inhibitor (HOE 077) prevents TIMP-1 gene expression in rat liver fibrosis."J Gastroenterol. 34. 376-377 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakaida I: "Herbal Medicine Sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet." Journal of Hepatology. 28. 298-306 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakaida I: "Interferon gamma treatment prevents procollagen gene expression without affecting TGF-βl expression in pig serum-induced rat liver fibrosis in vivo." Journal of Hepatology. 28. 471-479 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakaida I: "Interferon ganma but not alfa treatment prevents fibrosis by inhibiting procollagen and tissue inhibitor of metalloproteinase-l gene expression in pig serum-induced rat liver fibrosis in vivo." Hepatology Research. 12. 59-67 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakaida I: "Fibrosis accelerates the development of enzyme-altered lesions in the rat liver." Hepatology. 28. 1247-1252 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakaida I: "Quantutative analysis of liver fibrosis and stellate cell changes in patients with chronic hepatitis C after interferon therapy." American Journal of Gastroenterology. (発表予定).

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakaida I: "The iron chelator deferoxamine reduces preneoplastic lesions In the liver induced by a choline-deficient L-amino acid defined dietin the rat." Digestive Disease and Science. (発表予定).

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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