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Molecular Target of Regenerative Pulmonary Medicine for Chronic Obstructive Pulmonary Disease

Research Project

Project/Area Number 23659431
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Research InstitutionNagoya University

Principal Investigator

HASEGAWA Yoshinori  名古屋大学, 医学系研究科, 教授 (20270986)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Naozumi  名古屋大学, 医学部附属病院, 病院講師 (30378020)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺の再生 / 低酸素 / PTEN / 組織微小環境 / 上皮間葉系移行 / EMT / 肺構成細胞 / 再生医療 / 肺傷害
Research Abstract

To accumulate the basic research findings for pulmonary tissueregeneration, we focused on the molecular analysis of the Epithelial-mesenchymal transition (EMT) and its reverse phenomenon (MET). One is Twist, and the other is the effects of prolonged tissue hypoxia on EMT. We found that persistent hypoxia induced de novo twist expression, causing repression of SP-D and acquisition of an EMT phenotype. Third is tissue microenvironment (TM). In TM, many kinds of signaling pathway, which PTEN negatively regulates, are activated. Nevertheless, whether or not persistent hypoxia could affect the PTEN activity remains elusive. In this study, persistent hypoxia caused a decrease in PTEN expression and an increase in p-PTEN/PTEN ration in alveolar cells in vitro and in vivo. These findings suggest that regulation ofprolonged tissue hypoxia and EMT might be important for tissue regeneration of the lung.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (22 results)

All 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (12 results) Book (1 results)

  • [Journal Article] Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells2012

    • Author(s)
      Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y
    • Journal Title

      Mol Carcinog

      Volume: 51 Pages: 400-10

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury2012

    • Author(s)
      Sakamoto K, Hashimoto N, Kondoh Y, Imaizumi K, Aoyama D, Kohnoh T, Kusunose M, Kimura M, Kawabe T, Taniguchi H, Hasegawa Y
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol.

      Volume: 303

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Emerging evidence of epithelial-to-mesenchymal transition in lung carcinogenesis2012

    • Author(s)
      Sato M, Shames DS, Hasegawa Y
    • Journal Title

      Respirology

      Volume: 17 Pages: 1048-59

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury.2012

    • Author(s)
      Sakamoto K, Hashimoto N, Kondoh Y, Imaizumi K, Aoyama D, Kohnoh T, Kusunose M, Kimura M, Kawabe T, Taniguchi H, Hasegawa Y.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 303(1) Issue: 1 Pages: L43-L53

    • DOI

      10.1152/ajplung.00061.2012

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging evidence of Epithelial-to-Mesenchymal Transition in lung carcinogenesis.2012

    • Author(s)
      Sato M, Shames DS, Hasegawa Y.
    • Journal Title

      Respirology.

      Volume: 印刷中 Issue: 7 Pages: 1048-1059

    • DOI

      10.1111/j.1440-1843.2012.02173.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the transcription factor twist in phenotype alteration throughe pithelial-mesenchymal transition in lung cancercells2011

    • Author(s)
      Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y.
    • Journal Title

      Mol Carcinog

      Volume: E1 Issue: 5 Pages: 1-11

    • DOI

      10.1002/mc.20802

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Attenuation of TGF-β-Stimulated Collagen Production in Fibroblasts by Quercetin-Induced HO-12011

    • Author(s)
      Nakamura T, Matsushima M, Hayashi Y, Shibasaki M, Imaizumi K, Hashimoto N, Shimokata K, Hasegawa Y, Kawabe T
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: 44(5) Issue: 5 Pages: 614-620

    • DOI

      10.1165/rcmb.2010-0338oc

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells stably transduced with a dominant-negative inhibitor of CCL2 greatly attenuate bleomycine-induced lung damage2011

    • Author(s)
      斎藤繁紀
    • Journal Title

      The American Journal of Pathology

      Volume: 179 Issue: 3 Pages: 1088-1094

    • DOI

      10.1016/j.ajpath.2011.05.027

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Capsaicinoids regulate airway anion transporters through Rho kinase- and cyclic AMP-dependent mechanisms2011

    • Author(s)
      Hibino Y
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: 45 Issue: 4 Pages: 684-691

    • DOI

      10.1165/rcmb.2010-0332oc

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Various effect of compensatory induction of PTEN wild against TGFβ-induced epithelial-mesenchymal transition (EMT) in epithelial cells2012

    • Author(s)
      Kusunose M, Hashimoto N, Kimura M, Hasegawa Y
    • Organizer
      The FASEB Summer Research Conference
    • Place of Presentation
      Saxtons River, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Compensatory induction of mutation of phosphorylation sites in PTEN inhibits hypoxia-induced epithelial-mesenchymal transition (EMT) in epithelial cells2012

    • Author(s)
      Kimura M, Hashimoto N, Kusunose M, Hasegawa Y
    • Organizer
      The FASEB Summer Research Conference
    • Place of Presentation
      Saxtons River, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Acute and persistent hypoxia differentially induces surfactant protein D modulation and epithelial-mesenchymal transition via hypoxia-inducible factor 1αand twist stimulation in acute lung injury/fibrosis2012

    • Author(s)
      Hashimoto N, Sakamoto K, Hasegawa Y
    • Organizer
      The 2012 American Thoracic Society (ATS) International Conference
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Compensatory induction of mutated phosphorylation sites in the PTEN C-terminal suppresses tumor growth in lung cancers in vivo2012

    • Author(s)
      Hashimoto N, Aoyama D, Sakamoto K, Hasegawa Y
    • Organizer
      The 2012 American Thoracic Society (ATS) International Conference
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Inhibition of TGFβ-induced phenotype alterations through epithelial-mesenchymal transition (EMT) in epithelial cells by gene mutation of phosphorylation sites in PTEN2012

    • Author(s)
      Hashimoto N, Kusunose M, Kimura M, Hasegawa Y
    • Organizer
      The FASEB Summer Research Conference
    • Place of Presentation
      Saxtons River, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Acute and persistent hypoxia differentially induces surfactant protein D modulation and epithelial-mesenchymal transition via hypoxia-inducible factor 1α and twist stimulation in acute lung injury/fibrosis.2012

    • Author(s)
      Naozumi Hashimoto
    • Organizer
      The 2012 American Thoracic Society (ATS) International Conference
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Compensatory induction of mutated phosphorylation sites in the PTEN C-terminal suppresses tumor growth in lung cancers in vivo.2012

    • Author(s)
      Naozumi Hashimoto
    • Organizer
      The 2012 American Thoracic Society (ATS) International Conference
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Inhibition of TGFβ-induced phenotype alterations through epithelial-mesenchymal transition (EMT) in epithelial cells by gene mutation of phosphorylation sites in PTEN.2012

    • Author(s)
      Naozumi Hashimoto
    • Organizer
      The FASEB Summer Research Conference,
    • Place of Presentation
      Saxtons River, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Various effect of compensatory induction of PTEN wild against TGFβ-induced epithelial-mesenchymal transition (EMT) in epithelial cells2012

    • Author(s)
      Kimiaki Kusunose
    • Organizer
      The FASEB Summer Research Conference,
    • Place of Presentation
      Saxtons River, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Compensatory induction of mutation of phosphorylation sites in PTEN inhibits hypoxia-induced epithelial-mesenchymal transition (EMT) in epithelial cells.2012

    • Author(s)
      Motohiro Kimura
    • Organizer
      The FASEB Summer Research Conference,
    • Place of Presentation
      Saxtons River, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Inhibition Of TGF-Beta-Induced Phenotype Alterations Through Epithelial-Mesenchymal Transition(EMT) In Lung Cancer By Gene Modulation Of Phosphorylations Sites In Tumor Suppressor Pten2011

    • Author(s)
      Aoyama D, Hashimoto N, Imaizumi K, Kohnoh T, Sakamoto K, Ogawa T, Hasegaya Y.
    • Organizer
      American Thoracic Society International Conference 2011 (ATS・2011)
    • Place of Presentation
      Denver,Colorado,USA
    • Related Report
      2011 Research-status Report
  • [Presentation] Modulated Expression Of Surfactant Protein D In Acute Lung Injury Might Be Associated With Epithelial-Mesenchymal Transition In Epithelial Cells.2011

    • Author(s)
      Sakamoto K, Hashimoto N, Imaizumi K, Taniguchi H, Kondoh Y, Kohnoh T, Aoyama D, Ogawa T,Hasegaya Y.
    • Organizer
      American Thoracic Society International Conference 2011 (ATS・2011)
    • Place of Presentation
      Denver,Colorado,USA
    • Related Report
      2011 Research-status Report
  • [Book] ガイドラインサポート ハンドブック 呼吸器感染症 (エビデンスと診療ガイドライン)2011

    • Author(s)
      長谷川好規 (編集者 河野 茂)
    • Total Pages
      391
    • Publisher
      医薬ジャーナル社
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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