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Elucidation of the pathomechanism of lung fibrosis from the viewpoint of cellular senescence and cytoskeletal organization

Research Project

Project/Area Number 16K15460
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Research InstitutionUniversity of Miyazaki

Principal Investigator

Nakazato Masamitsu  宮崎大学, 医学部, 教授 (10180267)

Co-Investigator(Kenkyū-buntansha) 柳 重久  宮崎大学, 医学部, 助教 (60404422)
坪内 拡伸  宮崎大学, 医学部, 助教 (60573988)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肺線維症 / 肺リモデリング / 細胞老化 / 細胞骨格 / Pten / RhoA / Ror2 / 肺線維症 肺リモデリング
Outline of Final Research Achievements

In this study, we investigated the roles of epithelial Pten in the pathogenesis of lung fibrosis by using lung epithelial-specific Pten deficient (Pten-KO) mice. Pten-KO mice showed increased cell senescence and enhanced p53 expressions in alveolar epithelial cells (AECs). Pten-KO mice also showed enhanced cellular senescence-associated secretory phenotype in the lungs, and Pten-KO mice at 30 weeks old showed enhanced lung architectural remodeling (increased mean linear intercept of alveoli and alveolar destruction index). Interestingly, AECs of Pten-KO mice showed impaired bipolar spindle formations. These results indicated that epithelial Pten deficiency causes accelerated cellular senescence of AECs through p53 upregulation and the impairment of bipolar spindle formations, and subsequently enhances lung architectural remodeling.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (5 results)

  • [Journal Article] The Impacts of Cellular Senescence in Elderly Pneumonia and in Age-Related Lung Diseases That Increase the Risk of Respiratory Infections2017

    • Author(s)
      Shigehisa Yanagi, Hironobu Tsubouchi, Ayako Miura, Ayako Matsuo, Nobuhiro Matsumoto and Masamitsu Nakazato
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 3 Pages: 503-503

    • DOI

      10.3390/ijms18030503

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical application of ghrelin for chronic respiratory failure2017

    • Author(s)
      Matsumoto N, Tsubouchi H, Imazu Y, Arimura Y, Yanagi S, Iiboshi H, Nakazato M.
    • Journal Title

      Endocrine Journal

      Volume: 64 Issue: Suppl. Pages: S1-S3

    • DOI

      10.1507/endocrj.64.S1

    • NAID

      130007307950

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ghrelin does not influence cancer progression in a lung adenocarcinoma cell line2017

    • Author(s)
      Tsubouchi H, Onomura H, Saito Y, Yanagi S, Miura A, Matsuo A, Matsumoto N, Nakazato M.
    • Journal Title

      Endocrine Journal

      Volume: 64 Issue: Suppl. Pages: S41-S46

    • DOI

      10.1507/endocrj.64.S41

    • NAID

      130007307940

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation2017

    • Author(s)
      Otsubo K, Goto H, Nishio M, Kawamura K, Yanagi S, et al
    • Journal Title

      Oncogene

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Early Cancer Diagnosis by the Detection of Cancer-derived Proteins in Urine by a Novel MRM Technique.2017

    • Author(s)
      Masamitsu Nakazato
    • Organizer
      3rd JAPAN-US Workshop for Cancer Research
    • Place of Presentation
      Arizona
    • Year and Date
      2017-03-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Development of early diagnostic biomarkers candidates of lung cancer and pancreatic cancer by the detection of cancer-derived protein fragments in urine using the original MRM method .2017

    • Author(s)
      中里雅光
    • Organizer
      AMED-ERDN Joint Workshop
    • Related Report
      2017 Annual Research Report
  • [Presentation] グレリン研究アップデート.2017

    • Author(s)
      中里雅光
    • Organizer
      第90回日本内分泌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of early diagnostic biomarkers candidates of lung cancer and pancreatic cancer by the detection of cancer-derived protein fragments in urine using the original MRM method .2017

    • Author(s)
      中里雅光
    • Organizer
      JPrS2017 15thJHUPO Conference
    • Related Report
      2017 Annual Research Report
  • [Presentation] The role of Pten in the cell-fate determination of epithelial cells in lung development.2016

    • Author(s)
      Ayako Miura, Hironobu Tsubouch Shigehisa Yanagi, Nobuhiro Matsumoto, and Masamitsu Nakazato
    • Organizer
      European Respiratory Society International Congress 2016
    • Place of Presentation
      United Kingdom, London EXCEL
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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