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Analysis of Hippo-YAP signaling pathway that regulates cell tension in liver formation

Research Project

Project/Area Number 17H03982
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Nishina Hiroshi  東京医科歯科大学, 難治疾患研究所, 教授 (60212122)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords肝臓 / 細胞張力 / MDCK細胞 / YAP / サイズ / 品質管理 / Hippo-YAP / FRET / 張力 / シグナル伝達系 / Hippo / バイオセンサー / 細胞排除 / 肝細胞
Outline of Final Research Achievements

Organs including the liver are grown and maintained at an appropriate size through cell proliferation. Elucidation of the molecular mechanism that controls the size and quality of organs is an important issue both in Japan and abroad. From the isolation and analysis of medaka mutants, we showed that the transcriptional co-activator YAP plays an essential role in 3D organogenesis via cell tension, and that activated YAP-expressing canine kidney epithelial cells (MDCK) induces pressure on adjacent cells and extrusion of YAP-expressing cells to the apical surface. In this study, we found that 1) YAP-dependent elimination of impaired hepatocytes in mouse livers, and 2) an essential role of prostaglandin E2 in YAP-dependent MDCK elimination.

Academic Significance and Societal Importance of the Research Achievements

器官のサイズ制御と品質管理の分子機構の解明は、国内外を通じて重要で興味深い研究課題である。がん原遺伝子産物YAPが、細胞数の調節を介して器官サイズ制御に関与するという発見は多くの研究者に驚きをもって迎えられた。我々はYAPが細胞張力の調節を介して3D器官形成に関与することを見出した。また、異常細胞の排除の調節を介して器官の品質管理の制御にも関与することを示唆した。以上の研究成果は、器官のサイズと品質を制御する分子機構の一端を解明した学術的意義がある。また、再生医学の基盤研究として社会的意義がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (22 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 10 results) Book (1 results)

  • [Journal Article] Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.2020

    • Author(s)
      Ishihara E, Nagaoka Y, Okuno T, Kofuji S, Ishigami-Yuasa M, Kagechika H, Kamimura K, Terai S, Yokomizo T, Sugimoto Y, Fujita Y, Suzuki A, Nishina H.
    • Journal Title

      Genes Cells.

      Volume: 25(3) Issue: 3 Pages: 197-214

    • DOI

      10.1111/gtc.12750

    • NAID

      120006873037

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Hippo-YAP Pathway Regulates 3D Organ Formation and Homeostasis2018

    • Author(s)
      Ishihara Erika、Nishina Hiroshi
    • Journal Title

      Cancers

      Volume: 10 Issue: 4 Pages: 122-122

    • DOI

      10.3390/cancers10040122

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Erratum: YAP determines the cell fate of injured mouse hepatocytes in vivo2017

    • Author(s)
      Miyamura Norio、Hata Shoji、Itoh Tohru、Tanaka Minoru、Nishio Miki、Itoh Michiko、Ogawa Yoshihiro、Terai Shuji、Sakaida Isao、Suzuki Akira、Miyajima Atsushi、Nishina Hiroshi
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 16017-16017

    • DOI

      10.1038/ncomms16146

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK72017

    • Author(s)
      Yamasaki T, Deki-Arima N, Kaneko A, Miyamura N, Iwatsuki M, Matsuoka M, Fujimori-Tonou N, Okamoto-Uchida Y, Hirayama J, Marth JD, Yamanashi Y, Kawasaki H, Yamanaka K, Penninger JM, Shibata S, Nishina H.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 7348-7348

    • DOI

      10.1038/s41598-017-07845-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells2017

    • Author(s)
      Matsudaira, T., K. Mukai, T. Noguchi, J. Hasegawa, T. Hatta, S. Iemura, T. Natsume, N. Miyamura, H. Nishina, J. Nakayama, K. Semba, T. Tomita, S. Murata, H. Arai, and T. Taguchi
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 651-651

    • DOI

      10.1038/s41467-017-01255-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation. Oncogene2017

    • Author(s)
      Otsubo K, Goto H, Nishio M, Kawamura K, Yanagi S, Nishie W, Sasaki T, Maehama T, Nishina H, Mimori K, Nakano T, Shimizu H, Mak TW, Nakao K, Nakanishi Y, Suzuki A
    • Journal Title

      Oncogene

      Volume: 印刷中 Issue: 29 Pages: 4201-4211

    • DOI

      10.1038/onc.2017.58

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Human Papillomavirus 16 E6 Upregulates APOBEC3B via the TEAD Transcription Factor.2017

    • Author(s)
      Mori S, Takeuchi T, Ishii Y, Yugawa T, Kiyono T, Nishina H, Kukimoto I.
    • Journal Title

      Journal of Virology

      Volume: 91 Issue: 6

    • DOI

      10.1128/jvi.02413-16

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR42017

    • Author(s)
      J. Negishi, Y. Omori, M. Shindo, H. Takanashi, S. Musha, S. Nagayama, J. Hirayama, H. Nishina, T. Nakakura, C. Mogi, K. Sato, F. Okajima, Y. Mochimaru, H. Tomura
    • Journal Title

      J. Recept. Signal Transduct. Res.

      Volume: 37 Issue: 4 Pages: 401

    • DOI

      10.1080/10799893.2017.1298130

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel YAP1 Activator, Identified by Transcription-Based Functional Screen, Limits Multiple Myeloma Growth2017

    • Author(s)
      Maruyama Junichi、Inami Kazutoshi、Michishita Fumiyoshi、Jiang Xinliang、Iwasa Hiroaki、Nakagawa Kentaro、Ishigami-Yuasa Mari、Kagechika Hiroyuki、Miyamura Norio、Hirayama Jun、Nishina Hiroshi、Nogawa Daichi、Yamamoto Kouhei、Hata Yutaka
    • Journal Title

      Molecular Cancer Research

      Volume: 16 Issue: 2 Pages: 197-211

    • DOI

      10.1158/1541-7786.mcr-17-0382

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] YAP is essential for 3D organogenesis withstanding gravity.2017

    • Author(s)
      Asaoka Y, Nishina H, Furutani-Seiki M.
    • Journal Title

      Dev Growth Differ.

      Volume: 59 Issue: 1 Pages: 52-58

    • DOI

      10.1111/dgd.12338

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] The Hippo-YAP Pathway Regulates liver size and homeostasis2019

    • Author(s)
      Hiroshi Nishina
    • Organizer
      The Cold Spring Harber Asia conference on Liver, Biology, Diseases & Cancer
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脊椎動物の3D器官形成と維持2019

    • Author(s)
      仁科 博史
    • Organizer
      国立医薬品食品衛生研究所
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 高次神経活動を制御するJNKシグナル2019

    • Author(s)
      仁科博史
    • Organizer
      第92回日本生化学大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 脊椎動物の3D器官形成と維持2019

    • Author(s)
      仁科博史
    • Organizer
      脊椎動物の3D器官形成と維持
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 肝臓の形成と維持機構2019

    • Author(s)
      仁科博史
    • Organizer
      市原明先生追悼シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] YAP acts as a stress sensor that induces elimination of injured hepatocytes2018

    • Author(s)
      Hiroshi Nishina
    • Organizer
      FASEB Fundamental Biology and Pathophysiology of the Liver
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Active Yes-associated protein (YAP) induces mammalian cell extrusion in vitro and in vivo2018

    • Author(s)
      Hiroshi Nishina
    • Organizer
      9th Xiamen Winter Symposium, Xiamen,China
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脊椎動物の3D器官構築と維持2018

    • Author(s)
      仁科博史
    • Organizer
      第29回加藤記念研究助成特別講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 異常肝細胞排除による品質管理機構の解明2018

    • Author(s)
      仁科博史
    • Organizer
      第25回肝細胞研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The Hippo-YAP pathway regulates 3D liver formation and homeostasis2018

    • Author(s)
      Hiroshi Nishina
    • Organizer
      86th LGS seminar
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] YAP determines the cell fate of injured mouse hepatocytes in vivo2017

    • Author(s)
      Hiroshi Nishina
    • Organizer
      The 2017 Cold Spring Harboe Asia Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 分子細胞生物学 第8版2019

    • Author(s)
      H. Lodishほか、榎森 康文、堅田 利明、須藤 和夫、富田 泰輔、仁科 博史、山本 啓一
    • Total Pages
      1108
    • Publisher
      東京化学同人
    • ISBN
      9784807909766
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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