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Analysis of the mechanism of angiogenesis regulated by fibrinolytic factors

Research Project

Project/Area Number 13670049
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionKinki University

Principal Investigator

MATSUO Osamu  Department of Physiology, Kinki University School of Medicine, Professor, 医学部, 教授 (40030879)

Co-Investigator(Kenkyū-buntansha) OKADA Kiyotaka  Department of Physiology, Kinki University School of Medicine, Assistant, 医学部, 助手 (20185432)
UESHIMA Shigeru  Department of Physiology, Kinki University School of Medicine, Assistant Professor, 医学部, 助教授 (30193791)
深尾 偉晴  近畿大学, 医学部, 助手 (70218874)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsfibrinolysis / u-PA / t-PA / plasminogen / knockout mouse / angiogenesis / gene expression / MMP-2 / 線溶系因子 / 創傷治癒モデル / カプセル / フィブリン / 線溶系 / 線溶系因子欠損マウス / 血管内皮細胞 / マトリックスメタロプロテアーゼ
Research Abstract

Double gene deficient mouse of the fibrinolytic factors, which lost two kinds of fibrinolytic genes, was produced by crossing single gene deficient mouse of fibrinolytic factor which we have already established. Double gene deficient mice produced were mouse which lost u-PA and u-PAR genes (u-PA/u-PAR double knockout mouse), that lost u-PA and t-PA genes (u-PA/t-PA double knockout mouse), that lost α2-AP and u-PA genes (α2-AP/u-PA double knockout mouse) and th at lost α2-AP and t-PA genes (α2-A P/t-PA double knocktout mouse). The present study was performed in accordance with the institutional guidelines.
When the hemispherical capsule, which had many holes, was transplanted to subcutaneous of u-PA/t-PA double knockout mouse, the MMP-2 activity of the granulation tissue, which adhered out side of capsule, was significantly lower than the wild-type mouse. On the other hand, the MMP-2 activity of the granulation tissue, which proliferated in the capsule, was significantly higher than the wild-type mouse.
The vascular endothelial cell in granulation tissue which adhered to the capsule in u-PA/t-PA double knockout mouse was fewer than the wild type mouse, and it was indicated that both u-PA and t-PA were involved in the angiogenesis. Since plasminogen is the substrate for u-PA and t-PA, it is suggested that the plasminogen is important for the angiogenesis. Therefore, regulation of expression of the plasminogen gene was examined using the primary cultured liver cell. In the low-density culture, the expression of plasminongen mRNA was decreased. However, in the high-density culure where one hepatocyte attached to another, decrease in plasminogen mRNA was not observed. Therefore, it is confirmed that the stimulation by cell-cell contact may play an important role to maintain the expression of plasminongen mRNA in hepatocytes.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Akao M.: "Cellular density regulation of plasminogen gene expression in mouse hepatocytes"Life Sci. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueshima S.: "Function of tissue-type plasminogen activator releaser on vascular endothelial cells and thrombolysis in vivo"Thromb Haemostasis. 87. 1069-1074 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuno H.: "Lack of α2-antiplasmin promotes pulmonary heart failure via over-release of VEGF after acute myocardial Infarction"Blood. 100. 2487-2493 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Luttun A.: "Loss of placental growth factor protects mice against vascular permeability in pathological conditions"Biochem Biophys Res Commun. 295. 428-434 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueshima S.: "The differences in thrombolytic effects of administrated recombinant t-PA between Japanese and Caucasians"Thromb Haemostasis. 87. 544-546 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuno H.: "Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice"Thromb Haemostasis. 87. 98-104 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akao M., Ueshima S., Okada K., Fukao H., Seki T., Ariga T., Matsuo O.: "Cellular density regulation of plasminogen gene expression in mouse hepatocytes"Life Sciences. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueshima S., Matsuno H., Hayashi M., Horibuchi K., Okada K., Fukao H., Uematsu T., Matsuo O.: "Function of tissue-type plasminogen activator releaser on vascular endothelial cells and thrombolysis in vivo"Thromb Haemostasis. 87(6). 1069-1074 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuno H., Kozawa O., Yoshimi N., Akamatsu S., Hara A., Mori H., Okada K., Ueshima S., Matsuo O., Uematsu T.: "Lack of α2-antiplasmin promotes pulmonary heart failure via over-release of VEGF after acute myocardial infarction"Blood. 100(7). 2487-2493 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Luttun A, Brusselmans K, Fukao H, Tjwa M, Ueshima S, Herbert JM, Matsuo O, Collen D, Carmeliet P, Moons L: "Loss of placental growth factor protects mice against vascular permeability in pathological conditions"Biochem Btophys Res Commun. 295(2). 428-434 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueshima S., Matsuo O.: "The differences in thrombolytic effects of administrated recombinant t-PA between Japanese and Caucasians"Thromb Haemostasis. 87(3). 544-546 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuno H., Kozawa O., Okada K., Ueshima S., Matsuo O., Uematsu T.: "Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice"Thromb Haemostasis. 87(1). 98-104 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akao M.: "Cellular density regulation of plasminogen gene expression in mouse hepatocytes"Life Sci. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueshima S.: "Function of tissue-type plasminogen activator releaser on vascular endothellal cells and thrombolysis in vivo"Thromb Haemostasis. 87・6. 1069-1074 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuno H.: "Lack of α2-antiplasmin promotes pulmonary heart failure via over-release of VEGF after acute myocardial infarction"Blood. 100・7. 2487-2493 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Luttun A.: "Loss of placental growth factor protects mice against vascular permeability in pathological conditions"Biochem Blophys Res Commun. 295・2. 428-434 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueshima S.: "The differences in thrombolytic effects of administrated recombinant t-PA between Japanese and Caucasians"Thromb Haemostasis. 87・3. 544-546 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuno H.: "Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice"Thromb Haemostasis. 87・1. 98-104 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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