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EGFR ligand as a new therapeutic target for lung injury and pulmonary fibrosis.

Research Project

Project/Area Number 18590858
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HAMADA Naoki  Kyushu University, Kyusyu University Hospital, Clinical Fellow (00423567)

Co-Investigator(Kenkyū-buntansha) KUWANO Kazuyoshi  Jikei University, School of Medicine, Department of Internal Medicine, Professor (40205266)
MAEYAMA Takashige  KYUSHU UNIVERSITY, Faculty of Medical Sciences, Assistant Professor (40380456)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordspulmonary fibrosis / lung injury / EGFR / apoptosis / amphiregulin
Research Abstract

(1). Expression of an EGFR Wand in idiopathic interstitial pneumonia.
Amphiregulin is transmembrane glycoprotein, which is a member of epidermal growth factor receptor ligand family. Amphiregulin levels in serum were significantly increased in patients with interstitial pneumonias, especially, in patients with idiopathic pulmonary fibrosis, compared with those of healthy controls. Amphiregulin level form patients with interstitial pneumonia whose lung function was more severe tended to be higher than those from patients whose lung function was in normal range.
(2). Expression of an EGFR ligand in bleomycin-induced pneumopathy in mice.
The expression of intrinsic amphirgulin in lung tissues was upregulated at14days after bleomycin instillation.
(3). Cell signaling pathway of EGFR ligand in bleomycin induced pneumopathy in mice.
Amphiregulin treatment enhances the activation of Akt and Erk in lung epithelial cells. Amphiregulin may play a protective role probably through the activation of survival signals in bleomycin-induced pneumopathy in mice.
(4). Effect of amphiregulin, an EGFR ligand, on bleomycin擁nduced pneumopathy in mice.
The administration of recombinant amphiregulin improved the survival rate and suppressed the degree of inflammation and fibrosis and the number of TUNEL positive cells in lung tissues.
(5). Role of EGFR, ligand in lung injury and pulmonary fibrosis.
Amphiregulin plays protective role in acute phase of lung injury and fibrosis by a reduction of apoptosis of lung epithelial cells. A mhiregulin also may stimulate over growth of fibroblast in lung lesion and promote pulmonary fibrosis at chronic phase.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (19 results)

All 2007 2006

All Journal Article (11 results) (of which Peer Reviewed: 4 results) Presentation (5 results) Book (3 results)

  • [Journal Article] Gene transfer of soluble transforming growth factor type II receptor byin vivo electroporation attenuates lung injury and fibrosis.2007

    • Author(s)
      Yamada M.
    • Journal Title

      Journal of Clinical Pathology 60(8)

      Pages: 916-920

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis.2007

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

      Journal of Clinical Pathology 60(8)

      Pages: 916-920

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis2007

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

      J Clin Pathol 60(8)

      Pages: 916-20

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis.2007

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

      Journal of Chincal Pothology 59 (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Doxycycline attenuated pulmonary fibrosis indued by bleomycin in mice.2006

    • Author(s)
      Fujita M.
    • 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
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Editorials. PTEN as anew agent in the fight against fobrogenesis.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
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Doxycycline attenuated pulmonary fibrosis indued by bleomycin in mice2006

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

      Antimicrobial Agents and Chemotherapy 50

      Pages: 739-743

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Editorials. PTEN as anew agent in the fight against fobrogenesis2006

    • Author(s)
      K. Kuwano
    • Journal Title

      Am J Respir Crit Care Med 173

      Pages: 5-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 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

      Pages: 739-743

    • Related Report
      2006 Annual Research Report
  • [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: 1097-100

    • NAID

      130000076430

    • Related Report
      2006 Annual Research Report
  • [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

    • Related Report
      2006 Annual Research Report
  • [Presentation] Symposium : Mechanisms of pulmonary fibrosis. Alveolar cell injury and apoptosis.2007

    • Author(s)
      Kuwano K.
    • Organizer
      European Respiratory Society Annual Congress 2007
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2007-09-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Symposium- Mechanisms of pulmonary fibrosis. Alveolar cell injury and apoptosis.2007

    • Author(s)
      K. Kuwano
    • Organizer
      European Respiratory Society Annual Congress 2007
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2007-09-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effect of amphiregulin on bleomycin-induced pneumopathy in mice.2006

    • Author(s)
      Maeyama T., et al.
    • Organizer
      11^<th> Congress of Asian Pacific Society of Respirology
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Attenuation of bleomycin-induced pneumopathy in mice by a proteasome inhibitor, MG132.2006

    • Author(s)
      Fukumoto J., et al.
    • Organizer
      11^<th> Congress of Asian Pacific Society of Respirology
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cytocrome c levels in serum and bronchoalveolar lavage fluid in lung injury.2006

    • Author(s)
      Kuwano K., et al.
    • Organizer
      European Respiratory Society Annual Congress 2006
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2006-09-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
      2007 Final Research Report Summary
  • [Book] Annual Review Respirology 2006.2006

    • Author(s)
      K. Kuwano
    • Total Pages
      8
    • Publisher
      CHUGAI-IGAKUSHA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Annual Review呼吸器20062006

    • Author(s)
      桑野和善
    • Total Pages
      8
    • Publisher
      中外医学社、東京
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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