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The role of coagulation factors in tissue remodeling associated with chronic inflammatory diseases of the lung.

Research Project

Project/Area Number 16590745
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionMie University

Principal Investigator

TAGUCHI Osamu  Mie University, School of Medicine, Research Associate, 医学部附属病院, 講師 (90197244)

Co-Investigator(Kenkyū-buntansha) GABAZZA Esteban  Mie University, School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (00293770)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsCoagulation system / Inflammatory cytokines / Lung fibrosis / Thrombin receptors / Hypofibrinolysis / Thrombin / Lung inflammatory disease / Animal models / 線溶系 / 気道リモデリング / 成長因子 / 実験動物モデル / 気管支喘息 / 肺線維症モデル / Th2サイトカイン / 気道過敏性 / 気管支喘息モデル / トロンビンレセプター / 肺障害 / 間質性肺疾患 / 喘息の発症
Research Abstract

Background : The coagulation and fibrinolysis systems play a critical role in the pathogenesis of chronic inflammatory lung diseases including bronchial asthma, pulmonary artery hypertension and lung fibrosis. The authors have previously demonstrated that patients with chronic inflammatory diseases of the lung show increased activation of the coagulation system with dysfunction of the anticoagulant protein C pathway. It has been also recently demonstrated that the protease-activated receptor-1 (PAR-1) is involved in cell activation and that the protective action of activated protein C is mediated by PAR-1.
Objective : In the present study, we hypothesized that PAR-1 and TAFI are involved in the mechanistic pathway of lung injury and fibrosis.
Method : To demonstrate our hypothesis, we induced and compared the degree of lung fibrosis in wild type mice and in mice with PAR-1 and thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency. Lung fibrosis was induced by treating the animals with bleomycin using subcutaneous osmotic minipumps ; the animals were sacrificed on the 3^<rd> week of bleomycin treatment.
Results : The results of this investigation showed that mice deficient in PAR-1 and TAFI have less collagen deposition as measured by the total lung content of collagen and hydroxyproline and less lung fibrotic changes as compared to their wild type counterparts. Measurement of inflammatory cytokines and growth factors was also performed in each group of mice. PAR-1 and TAFI knockout mice showed significantly decreased bronchoalveolar lavage fluid concentrations of TNF-α, IL-1β, TGF-β1 and thrombin-antithrombin complex as compared to wild type mice.
Conclusion : Overall, the results of this study showed that both PAR-1 and TAFI are involved in the pathogenesis of lung injury and fibrosis.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (20 results)

All 2006 2005 2004

All Journal Article (18 results) Book (2 results)

  • [Journal Article] Thrombin-activatable fibrinolysis inhibitor deficiency attenuates bleomycin-induced lung fibrosis.2006

    • Author(s)
      Hajime Fujimoto
    • Journal Title

      American Journal of Pathology 168:4(印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thrombin-activatable fibrinolysis inhibitor deficiency attenuates bleomycin-induced lung fibrosis.2006

    • Author(s)
      Fujimoto H
    • Journal Title

      Am J Pathol 168(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thrombin-activatable fibrinolysis inhibitor deficiency attenuates bleomycin-induced lung fibrosis.2006

    • Author(s)
      Hajime Fujimoto
    • Journal Title

      American Journal of Pathology 168 : 4(印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Anti-inflammatory effect of activated protein C in gastric epithelial cells.2005

    • Author(s)
      Misaki Nakamura
    • Journal Title

      Journal of Thrombosis and Haemostasis 3:12

      Pages: 2721-2729

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vacuolating cytotoxin A is associated with invreased thrombin generation in gastric mucosa.2005

    • Author(s)
      Yuko Suzuki
    • Journal Title

      Helicobaster 10:4

      Pages: 323-331

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-inflammatory effect of activated protein C in gastric epithelial cells.2005

    • Author(s)
      Nakamura M
    • Journal Title

      J Thromb Haemost 3

      Pages: 2721-2729

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vacuolating cytotoxin A is associated with increased thrombin generation in gastric mucosa.2005

    • Author(s)
      Suzuki Y
    • Journal Title

      Helicobaster 10

      Pages: 323-331

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-inflammatory effect of activated protein C in gastric epithelial cells.2005

    • Author(s)
      Misaki Nakamura
    • Journal Title

      Journal of Thrombosis and Haemostasis 3 : 12

      Pages: 2721-2729

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Vacuolating cytotoxin A is associated with increased thrombin generation in gastric mucosa.2005

    • Author(s)
      Yuko Suzuki
    • Journal Title

      Helicobaster 10 : 4

      Pages: 323-331

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse2004

    • Author(s)
      Esteban C Gabazza
    • Journal Title

      Pathology International 54:10

      Pages: 774-780

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] protective role of activated protein C in lung and airway remodeling2004

    • Author(s)
      Koji Suzuki
    • Journal Title

      Critical Care Medicine 32:5

      Pages: 262-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Progress in the understanding of protease-activated receptors.2004

    • Author(s)
      Esteban Gabazza
    • Journal Title

      International Journal of Hematology 79:2

      Pages: 117-122

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Progress in the understanding of protease-activated receptors.2004

    • Author(s)
      Gabazza EC
    • Journal Title

      Int J Hematol 79

      Pages: 177-122

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protective role of activated protein C in lung and airway remodeling.2004

    • Author(s)
      Suzuki K
    • Journal Title

      Crit Care Med 32

      Pages: 262-265

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of a novel human protein C inhibitor (PCI) gene transgenic mouse useful for studying the role of PCI in physiological and pathological conditions.2004

    • Author(s)
      Tatsuya Hayashi
    • Journal Title

      Journal of Thrombossis and Haemostasis 2:6

      Pages: 949-961

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Protective role of activated protein C in lung and airway remodeling2004

    • Author(s)
      Koji Suzuki
    • Journal Title

      Critical Care Medicine 32:5

      Pages: 262-265

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice.2004

    • Author(s)
      Hisamichi Yuda
    • Journal Title

      Blood 103:6

      Pages: 2196-21204

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Do matrix metalloproteinases protect or worsen pneumonia?2004

    • Author(s)
      Esteban Gabazza
    • Journal Title

      American Journal of Respiratory and Critical Care Medicine 169:1

      Pages: 133-133

    • Related Report
      2004 Annual Research Report
  • [Book] Encyclopeida of Respiratory Medicine2006

    • Author(s)
      Esteban Gabazza
    • Publisher
      Elsevier社(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Encyclopedia of Respiratory Medicine : Protein C and Protein S2006

    • Author(s)
      Esteban Gabazza
    • Publisher
      Elsevier社(印刷中)
    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2021-04-07  

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