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Escape from Inhibition of Liver Regeneration in Fibrotic Liver through The Modulation of Extracellular Matrix.

Research Project

Project/Area Number 07670637
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionUniversity of Occupational and Environmental Health

Principal Investigator

YAMADA Shinwa  University of Occupational and Environmental Health Health Sciences, Professor, 産業保健学部, 教授 (60143426)

Co-Investigator(Kenkyū-buntansha) TANAKA Yoshiya  University of Occupational and Environmental Health Medicine, Assist. Professor, 医学部, 講師 (30248562)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsextracellular matrix / liver regeneration / liver fibrosis / hepatocyte growth factor / transforming growth factor / hepatic necrosis / 肝再生 / TGFβ / HGF
Research Abstract

Ithas been well known that the liver has a great potential to regenerate. The fibrotic liver, however, has been demonstrated to regenerate more slowly and to less extent that the healthy control. The mechanism of the attenuation was unclear. We have examined whether the inhibition of regeneration in fibrotic liver is due to hepatocyte growth factor (HGF) -trapping on the accumulated extracellular matrix by the action of transforming growth factor (TGF) -beta1.
We evaluated the spatial relationship between TGF-beta1 expression and liver regeneration in rat fibrotic liver with or without acute hepatocellular necrosis after partial hepatecomy. Male Fisher rats were given repeatedly pork serum (0.5 ml/100g WB) for 4 months until liver fibrosis was developed. A single dose of carbon tetrachloride (CCl4 : 0.1ml/100g BW) was injected to one group of the rats. When the expression of TGF-beta1 was observed with using the polyclonal antibody after tow-lobe hepatectomy, its expression around the s … More eptal fibrosis was enhanced and peaked at 48 h. The degree of its expression was significantly higher than regenerating liver of normal control rats. In the rats complicated with an acute hepatic necrosis (CCl4), TGF-beta1 was induced around the necrotic area and it was expressed on the stellate-shaped cells which were assessed as Kupffer cells. When the localization of S-phase hepatocytes in the hepatic lobule was evaluated with using BrdU,the regeneration around the septal fibrotic areas, except the area in close to the blood vessels, was assessed to be low. In the rats complicated with an acute hepatic necrosis, the BrdU labeling index and ^3H-thymidine uptake were significantly (P<0.05) lower as compared with those uncomplicated with the necrosis. These findings suggested that TGF-beta1 trapped on the extracellular matrix contributes at least as a part to the inhibition of regeneration in the fibrotic livers.
We are prompted to further investigate the extra-and intracellular signal transduction of this inhibitory action. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Sugita,H.: "Enhanced expression of cytokine-induced neutrophil chemoattractant (CINC) by bronchoalveolar macrophages in celulein-induced pancreatitis rats." Dig. Dis. Sci.42. 154-160 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,Y.: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells." J. Exp. Med.184. 1987-1997 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisama,N.: "Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver." Dig. Dis. Sci.41. 1481-1486 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama,Y.: "Cross-linking of intercellular adhesion molecule-1 (CD54) induces AP-1 activation and interleukin-1b transcription." J. Immunol.157. 5097-5103 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,Y.: "Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1." J. Bone Miner. Res.10. 1462-1469 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wake,A.: "Calcium-dependent homotypic adhesion through LFA-1/ICAM-1 induces interleukin-1 and PTHrP production on adult T-cell leukemia cells in vitro." Blood. 86. 2257-2267 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugita, H., Yamaguchi, Y., Ikei, S., Yamada, S., Ogawa, M.: "Enhanced expression of cytokine-induced neutrophil chemoattractant (CINC) by bronchoalveolar macrophages in celulein-induced pancreatitis rats." Dig. Dis. Sci.Vol. 42 Nol. 1. 154-160 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Kimata, K., Wake, A., Mine, S., Morimoto, I., Yamakawa, N., Habuchi, H., Ashikari, S., Yamamoto, H., Sakurai, K., Yoshida, K., Suzuki, S., Eto, S.: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells." J.Exp. Med.Vol. 184. 1987-1997 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisama, N., Yamaguchi, Y., Okajima, K., Uchida, M., Murakami, K., Mori, K., Yamada, S., Ogawa, M.: "Anticoagulant pretreatment attenuates production of cytokineinduced neutrophil chemoattractant following ischemiareperfusion of rat liver." Dig. Dis. Sci.Vol. 41 No. 7. 1481-1386 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koyama, Y., Tanaka, Y., Saito, K., Abe, M., Nakatsuka, K., Morimoto, I., Auron, P.E., Eto, S.: "Cross-linking of intercellular adheson molecule-1 (CD54) induces AP-1 activation and interleukin-1b transcription." J.Immunol.Vol. 157. 5097-5103 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, Y., Morimoto, I., Nakano, Y., Okada, Y., Hirota, S., Nomura, S., Nakamura, T., Eto, S.: "Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1." J.Bone Miner. Res.Vol. 10. 1462-1469 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wake, A., Tanaka, Y., Nakatsuka, K., Misago, M., Oda, S., Morimoto, I., Eto, S.: "Calcium-dependent homotypic adhesion through LFA-1/ICAM-induces interleukin-1 and PTHrP production on adult T-cell leukemia cells in vitro." Blood. Vol. 86. 12257-2267 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugita,H.: "Enhanced expression of cytokine-induced neutrophil chemoattractant (CINC) by bronchoalveolar macrophages in celulein-induced pancreatitis rats." Dig.Dis.Sci.42. 154-160 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,Y.: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endothelial cells." J.Exp.Med.184. 1987-1997 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hisama,N.: "Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver." Dig.Dis.Sci.41. 1481-1486 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koyama,Y.: "Cross-linking of intercellular adhesion molecule-1 (CD54) induces AP-1 activation and interleukin-1b transcription." J.Immunol.157. 5097-5103 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,Y.: "Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1." J.Bone Miner.Res.10. 1462-1469 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Wake,A.: "Calcium-dependent homotypic adhesion through LFA-1/ICAM-1 induces interleukin-1 and PTHrP production on adult T-cell leukemia cells in vitro." Blood. 86. 2257-2267 (1995)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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