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Significance of adhesion molecules in hepatic fibrosis.

Research Project

Project/Area Number 03670381
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionThe Jikei University School of Medicine

Principal Investigator

YAMAUCHI Masayoshi  The Jikei University School of Medicine, 1st Dept of Med.Assistant Professor, 医学部, 講師 (20138811)

Co-Investigator(Kenkyū-buntansha) MIZUHARA Yuji  The Jikei University School of Medicine, 1st Dept of Med., Assistant
OHATA Mituru  The Jikei University School of Medicine, 1st Dept of Med., Assistant (50231204)
HIRAKAWA Junnichi  The Jikei University School of Medicine, 1st Dept of Med., Assistant (00231548)
NAKAJIMA Hisato  The Jikei University School of Medicine, 1st Dept of Med., Assistant (90207788)
TODA Gotaro  The Jikei University School of Medicine, Ist Dept of Med.Professor, 医学部, 教授 (40090500)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsHepatic fibrosis / Integrin / Adhesion molecule / ICAM-1 / VCAM-1 / Fibronectin receptor / Vitronectin receptor / VNR / ICAM‐1 / VCAM‐1 / Fibronectin receptor / Vitronectin receptor / Fibronectin / Vitvonectin receptor / Integvin supenfamily
Research Abstract

The Adhesion molecules such as integrin subfamilies are engaged in interactions with various extracellular matrix components such as collagen, laminin, fibronectin and vitronectin. In this study, we clarified the significance of adhesion molecules in patients with hepatic fibrosis.
1. Pooles sera collected from cirrhotic patients was fractionated by affinity chromatography with monoclonal antibodies against integrin beta 1 and beta 3. Western immunoblotting of eluates showed that integrin beta 1 and beta 3 were present in human serum.
2. We developed sandwich enzyme-linked immunosorbent assay (ELISA) for integrin beta 1 or beta 3. The serum level of integrin was significantly higher in patients with chronic active hepatitis, liver cirrhosis when compared with healthy subjects. The increase in the serum level of integrin beta 1 was associated with the severity of liver diseases, especially with the hepatic fibrosis. The serum level of integrin beta 3 also increased in patients with chroni … More c liver diseases. However, no correlation was observed between serum levels of integrin beta 3 and the degree of fibrosis, necrosis or degeneration. Immunohistochemicalstudies showed that a strong staining for integrin beta 1 was evident on fibrotic areas, and on the plasma membranes of hepatocytes and sinusoidal lining cells. Integrin beta 3 was expressed in sinusoidal lining cells, platelets, vascular endothelial cells and arterial walls and on the plasma membranes of hepatocytes. However, no anti- beta 3 staining was present in fibrotic area. In conclusion, the serum level of integrin beta 1 in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.
3. Human platelets also contain a vitronectin receptor ( alpha v beta 3). We revealed that integrin beta 3 of platelet was significantly higher in chronic hepatitis and liver cirrhosis than in the healthy subjects.
4. Serum levels of intercellular adhesion molecule-1 (ICAN-1), a ligand for alpha L beta 2(LFA-1) and vascular adhesion molecule-1 (VCAM-1), a ligand for alpha 4 beta 1 (VLA-4), were significantly higher in the patients with alcoholic hepatitis and cirrhosis than in the non-ciirhotic alcoholic liver disease and the healthy subjects. Furthermore, only the serum level of ICAM-1 was significantly higher in the patients with alcoholic hepatitis than in those with alcoholic cirrhosis. These data showed that ICAM-1/LFA-1 interaction may be more important in the development of alcoholic hepatitis. Less

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] M.Yamauchi,et al.: "Serum vitronectin receptor in alcoholic liver disease:correlation with fibronectin receptor and morphological features." Alcohol & Alcoholism. 28. 37-43 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Yamauchi,et al.: "Increased in serum β_3 integrin in patients with chronic liver disease" Clinica Chimica Acta. (印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Shimada,et al: "Serum levels of intercellular adhesion molecule-1 in patients with alcoholic liver disease" Alcohol & Alcoholism. (印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 島田青佳,他: "アルコール性肝炎における血清Intercellular adhesion molecule-1(ICAM-1)濃度の意義" アルコールと医学生物学. 13. 108-113 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Yamauchi,et al: "Serum levels of integrins in chronic liver disease" Pathology up date. (印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Yamauchi,et al: "Serum tenasein levels in chronic liver disease" Liver. (印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Yamauchi,et al: "Serumritronetin neceptor in alecholic liver dislise correlation with fibronectin reaptor and morpbological feafures" Alcohol & Alcohslism. 28. 37-43 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 島田青佳,他: "アルコール性肝炎における血清Intercellnlpr adhesion molecrler(ZCAM‐1)濃度の意義" アルコールと医学生物学. 13. 108-113 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Yamauchi et al: "Incrersed in serum beta_3 integrm in patients with chronic liver diserse" Clinica chimica Acta. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Shimada,et al: "Serum levels of intercellnler adlusion molechle‐1 in prffents with alcoholit liver chiaerse" Alohol & Alohslism. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Yamauchi,et al: "Serum levels in chronic liver chisease" Liver. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 山内 眞義他: "アルコール性肝障害におけるVitronectin receptorの意義" アルコール代謝と肝. 12. 69-73 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Yamuchi etal: "Serum vitronectin receptor in alcoholic liver disease:correlntion with fibronectin recepton and morphological futures" Alcohol&Alcoholism. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Yamuchi etal: "Serum levels of integris in chronic liver disease" Patholozy update. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山内 眞義 他: "慢性肝疾患における血清Fibronectin Receptorの意義" 日本臨床代謝学会記録. 27. 96-97 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Masayoshi Yamauch et al,: "Petection of fibronectin receptor ingera:Its Clinical Significance as a parameter of hepatic fibrosis" Hepatology. 14(2). 244-250 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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