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Investigation and regulation of molecular mechanisms of epithelial mesenchymal transition in pulmonary fibrosis

Research Project

Project/Area Number 17590793
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKYUSHU UNIVERCITY

Principal Investigator

KUWANO Kazuyoshi  Kyushu University, Graduate School of Medical Sciences, Associate Professor, 大学院医学研究院, 助教授 (40205266)

Co-Investigator(Kenkyū-buntansha) FUJITA Masaki  Kyushu University, Hospital, Research associate, 大学病院, 助手 (50325461)
MAEYAMA Takashige  Kyushu University, Hospital, Medical Staff, 大学病院, 医員 (40380456)
吉見 通洋  九州大学, 大学病院, 助手 (30372759)
猪島 一朗  九州大学, 大学病院, 医員 (90380419)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordspulmonary fibrosis / lung injury / EMT / apoptosis / bleomycin / TGF-beta / 特発性間質性肺炎 / 特発性肺線維症
Research Abstract

Epithelial-mesenchymal transition (EMT) has been considered to be involved in organ fibrogenesis. However, there is few direct evidence of this process in the pathophysiology of pulmonary fibrosis in vivo. Therefore, we tried to verify the involvement of this process in the development of pulmonary fibrosis. Since the co-expressions of epithelial and mesenchymal markers are thought to be a marker of EMT, we performed dual immunohistochemistry to assess the co-expressions of these proteins in lung tissues from bleomycin-induced pulmonary fibrosis in mice, and from patients with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Double positive cells for epithelial markers including E-cadherin, CD44v10,T1α, or aquaporin 5,and a mesenchymal marker α-smooth muscle actin were rarely found in bleomycin-induced pulmonary fibrosis in mice. Double positive cells for E-cadherin, ICAM-1,LEA, CD44v9,or SP-A and a-smooth muscle actin were not found in lung tissues from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. In contrast to few incidence of EMT, we occasionally found intermediate cells which have characteristics of type I and type II or bronchiolar epithelial cells. These results suggest that EMT may be present in pulmonary fibrosis, but have minor role in the pathophysiology of pulmonary fibrosis.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (19 results)

All 2006 2005

All Journal Article (18 results) Book (1 results)

  • [Journal Article] Doxycycline attenuated pulmonary fibrosis induced by bleomycin in mice.2006

    • Author(s)
      Fujita M, Kuwano K, et al.
    • Journal Title

      Antimicrobial Agents and Chemotherapy 50

      Pages: 739-743

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis.2006

    • Author(s)
      Yamada M, Kuwano K et al.
    • Journal Title

      Journal of Clincal Pathology 59(In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A pregnant woman with complications of lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura.2006

    • Author(s)
      Toyoda K, Kuwano K, et al.
    • Journal Title

      Internal Medicine 45

      Pages: 1097-1100

    • NAID

      130000076430

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Editorials. PTEN as a new agent in the fight against fibrogenesis.2006

    • Author(s)
      Kuwano K
    • Journal Title

      Am J Respir Crit Care Med 173

      Pages: 5-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis.2006

    • Author(s)
      Yamada M, Kuwano K, Maeyama T, Yoshimi M, Hamada N, Fukumoto J, Egashira K, Hiasa K, Takayama K, Nakanishi Y.
    • Journal Title

      J Clin Pathol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Doxycycline attenuated pulmonary fibrosis induced by bleomycin in mice.2006

    • Author(s)
      Fujita M, Ye Q, Ouchi H, Harada E, Inoshima I, Kuwano K, Nakanishi Y
    • Journal Title

      Antimicrobial Agents Ch 50

      Pages: 739-743

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A pregnant woman with complications of lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura.2006

    • Author(s)
      Toyoda K, Matsumoto K, Inoue H, Komori M, Fujita M, Hashimoto S, Kuwano K, Nakanishi Y.
    • Journal Title

      Intern Med. 45

      Pages: 1097-100

    • NAID

      130000076430

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Doxycycline attenuated pulmonary fibrosis induced by bleomycin in mice.2006

    • Author(s)
      Fujita M., Kuwano K, et al.
    • Journal Title

      Antimicrobial Agents and Chemotherapy 50

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis.2006

    • Author(s)
      Yamada M, Kusano K et al.
    • Journal Title

      Journal of Clincal Pathology 59(In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A pregnant woman with complications of lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura.2006

    • Author(s)
      Toyoda K, Kusano K, et al.
    • Journal Title

      Internal Medicine 45

      Pages: 1097-100

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 肺線維症におけるアポトーシスの役割2006

    • Author(s)
      桑野和善, 吉見通洋, 中西洋一
    • Journal Title

      呼吸と循環 54

      Pages: 43-48

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PTEN as a new agent in the light against fibrogenesis (editorials)2006

    • Author(s)
      Kuwano K
    • Journal Title

      Am J Respir Crit Care Med 173

      Pages: 5-6

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Doxycycline attenuates puimonary fibrosis induced by bleomycin in mice2006

    • Author(s)
      Fujita M, Kuwano K, et al.
    • Journal Title

      Antimicrobial Agents Ch 50

      Pages: 739-743

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice.2005

    • Author(s)
      Hamada N, Kuwano K, et al.
    • Journal Title

      Journal of Immunology 175

      Pages: 1224-1231

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The p53-Mdm2 association in epithelial cells in idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.2005

    • Author(s)
      Nakashima N, Kuwano K, et al.
    • Journal Title

      Journal of Clinical Pathology 58

      Pages: 583-589

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice.2005

    • Author(s)
      Hamada N, Kuwano K, Yamada M, Hagimoto N, Hiasa K, Egashira K, Nakashima N, Maeyama T, Yoshimi M, Nakanishi Y.
    • Journal Title

      J Immunol 175

      Pages: 1224-1231

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The p53-Mdm2 association in epithelial cells in idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.2005

    • Author(s)
      Nakashima N, Kuwano K, Maeyama T, Hagimoto N, Yoshimi M, Hamada N, Yamada M, Nakanishi Y.
    • Journal Title

      J Clin Pathol 58

      Pages: 583-589

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice2005

    • Author(s)
      Hamada N, Kuwano K, et al.
    • Journal Title

      J Immunol 175

      Pages: 1224-1231

    • Related Report
      2005 Annual Research Report
  • [Book] Annual Review 呼吸器 20062006

    • Author(s)
      桑野和善
    • Total Pages
      8
    • Publisher
      中外医学社、東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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