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A role of Hippo pathway in pulmonary diseases

Research Project

Project/Area Number 16K09575
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

Mitani Akihisa  東京大学, 保健・健康推進本部, 助教 (90739137)

Co-Investigator(Kenkyū-buntansha) 漆山 博和  東京大学, 医学部附属病院, 助教 (20725303)
寺崎 泰弘  日本医科大学, 医学部, 准教授 (50332870)
田中 剛  東京大学, 医学部附属病院, 講師 (50456133)
田宮 浩之  東京大学, 医学部附属病院, 助教 (50722071)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsHippo pathway / TAZ / YAP / 肺発生 / COPD / 遺伝子改変マウス / Hippo シグナル / hippoシグナル / Hippoシグナル / 発生・分化 / 病理学 / 内科 / 動物
Outline of Final Research Achievements

We showed that TAZ and its homolog YAP are required in the different stages of lung development, using lung epithelial specific conditional knockout mice. TAZ conditional knockout mice had emphysema-like lung phenotype. We also revealed that Shh-Fgf10 pathway is regulated by YAP in lung development.
Immunohistochemistry showed the decreased expression of Shh and the increased expression of Fgf10 in YAP conditional knockout lungs, and organ culture revealed the administration of Shh improved their phenotype. In vitro studies also showed that the expression of Shh was stimulated by YAP.

Academic Significance and Societal Importance of the Research Achievements

慢性閉塞性肺疾患(COPD)は、気道の慢性炎症と気道閉塞を主症状とする難治性の疾患である。気管支拡張薬を中心とした対照的な治療が中心であり、新しい治療ターゲットの発見が望まれる。
近年、COPDの病因として、肺発生の異常が注目を集めるようになってきた。我々はこれまでにTAZノックアウトマウスが、肺気腫様の表現型を持つことを示したが、本研究によって肺上皮特異的コンディショナルKOマウスでも同様の表現型となることを示した。また、TAZやYAPの肺発生における役割についてより詳細な解析を行った。これらの発見は、肺発生やCOPDの病態の理解をより深めるものである。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2020 2019 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Epithelial Expression of YAP and TAZ Is Sequentially Required in Lung Development2020

    • Author(s)
      Isago Hideaki、Mitani Akihisa、Mikami Yu、Horie Masafumi、Urushiyama Hirokazu、Hamamoto Ryuji、Terasaki Yasuhiro、Nagase Takahide
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 62 Issue: 2 Pages: 256-266

    • DOI

      10.1165/rcmb.2019-0218oc

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] The Hippo pathway effectors TAZ and YAP are sequentially required in lung development2019

    • Author(s)
      Isago H, Mitani A, Terasaki Y, Nagase T.
    • Organizer
      29th International Congress of the European Respiratory Society (ERS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hippo pathway effectors Taz and Yap functioning at different stages of lung development2017

    • Author(s)
      H. Isago, A. Mitani, Y. Mikami, H. Urushiyama, H. Tamiya, S. Noguchi, A. Saito, T. Jo, Y. Yamauchi, G. Tanaka, and T. Nagase
    • Organizer
      APSR 2017 Congress
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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