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Elucidation of osmo-physiology through analysis where and how osmotic circumstance functions in the body

Research Project

Project/Area Number 18H02569
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionThe University of Tokyo

Principal Investigator

Naguro Isao  東京大学, 大学院薬学系研究科(薬学部), 准教授 (80401222)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
KeywordsOsmo-physiology / 浸透圧 / ASK3 / LLPS / NFAT5 / 細胞代謝 / マクロファージ / 代謝変化 / osmo-physiology / 脂質分子
Outline of Final Research Achievements

In this project, I investigated the importance of osmotic environment for organisms in a viewpoint of molecular biology and found several new molecular mechanisms that govern ASK3 signaling, gene expression via NFAT5 and cellular metabolism in osmotic stress conditions. These our results will contribute to figure out the molecular basis by which cells recognize and respond to osmotic stress, and help to link osmotic environment to immune cell regulation in certain inflammatory diseases.

Academic Significance and Societal Importance of the Research Achievements

特に哺乳類細胞では、浸透圧という物理量がどのような分子メカニズムで感知され、生理応答につながるか未解明な部分が残されているが、本研究によりリン酸化シグナル伝達、遺伝子発現、細胞代謝という複数の階層における浸透圧応答メカニズムが明らかになった。近年、高食塩食は高血圧のみならず、自己免疫疾患など炎症性疾患の増悪要因になることがわかりつつあるが、本研究の結果は、高食塩食のような体内浸透圧環境が変化するストレスが生体にどのように影響を与えるか理解し、薬などにより悪影響を取り除くための基盤的知見になると期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(35 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (20 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] University of California Berkeley(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of California Berkeley(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose)2021

    • Author(s)
      Watanabe Kengo、Morishita Kazuhiro、Zhou Xiangyu、Shiizaki Shigeru、Uchiyama Yasuo、Koike Masato、Naguro Isao、Ichijo Hidenori
    • Journal Title

      Nat. Commun.

      Volume: 12 Pages: 1353-1353

    • DOI

      10.1038/s41467-021-21614-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mitochondrial Ca2+ uptake regulator, MICU1, is involved in cold stress‐induced ferroptosis2021

    • Author(s)
      Nakamura Toshitaka、Ogawa Motoyuki、Kojima Kazuki、Takayanagi Saki、Ishihara Shunya、Hattori Kazuki、Naguro Isao、Ichijo Hidenori
    • Journal Title

      EMBO Rep.

      Volume: 22

    • DOI

      10.15252/embr.202051532

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASK1 suppresses NK cell-mediated intravascular tumor cell clearance in lung metastasis.2021

    • Author(s)
      Fujimoto, M., Kamiyama, M., Fuse, K., Ryuno, H., Odawara, T., Furukawa, N., Yoshimatsu, Y., Watabe, T., Michaela, P.-M., Veronika, S., Tahara, H., Hayakawa, Y., Sato, T., Takeda, K., Naguro, I. and Ichijo, H.
    • Journal Title

      Cancer Sci.

      Volume: 112 Pages: 1633-1643

    • DOI

      10.1111/cas.14842

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] FGF21 Induced by the ASK1-p38 Pathway Promotes Mechanical Cell Competition by Attracting Cells2021

    • Author(s)
      Ogawa Motoyuki、Kawarazaki Yosuke、Fujita Yasuyuki、Naguro Isao、Ichijo Hidenori
    • Journal Title

      Curr. Biol.

      Volume: 31 Pages: 1048-1057

    • DOI

      10.1016/j.cub.2020.11.052

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis2021

    • Author(s)
      Kojima Kazuki、Ichijo Hidenori、Naguro Isao
    • Journal Title

      J. Biochem.

      Volume: in press Pages: 395-407

    • DOI

      10.1093/jb/mvaa145

    • NAID

      40022588047

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osmotic gradients induce stable dome morphogenesis on extracellular matrix2020

    • Author(s)
      Ishida-Ishihara Sumire、Akiyama Masakazu、Furusawa Kazuya、Naguro Isao、Ryuno Hiroki、Sushida Takamichi、Ishihara Seiichiro、Haga Hisashi
    • Journal Title

      J. Cell Sci.

      Volume: 133 Pages: 243865-243865

    • DOI

      10.1242/jcs.243865

    • NAID

      120007124455

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASK1 promotes uterine inflammation leading to pathological preterm birth2020

    • Author(s)
      Yoshikawa Midori、Iriyama Takayuki、Suzuki Kensuke、Sayama Seisuke、Tsuruga Tetsushi、Kumasawa Keiichi、Nagamatsu Takeshi、Homma Kengo、Naguro Isao、Osuga Yutaka、Ichijo Hidenori、Fujii Tomoyuki
    • Journal Title

      Sci. Rep.

      Volume: 10 Pages: 1887-1887

    • DOI

      10.1038/s41598-020-58653-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide siRNA screening reveals that DCAF4-mediated ubiquitination of optineurin stimulates autophagic degradation of Cu/Zn superoxide dismutase.2020

    • Author(s)
      Homma, K., Takahashi, H., Tsuburaya, N., Naguro, I., Fujisawa, T. and Ichijo, H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Pages: 3148-3158

    • DOI

      10.1074/jbc.ra119.010239

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In situ single-cell western blot on adherent cell culture.2019

    • Author(s)
      Zhang, Y., Naguro, I. and Herr, A.
    • Journal Title

      Angew. Chem. Int. Ed. Engl.

      Volume: 58 Pages: 13929-13934

    • DOI

      10.1002/anie.201906920

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases.2019

    • Author(s)
      Nakamura, T., Naguro, I. and Ichijo, H.
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: pii Pages: 1398-1409

    • DOI

      10.1016/j.bbagen.2019.06.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Staphylococcus aureus aggregation in the plasma fraction of silkworm hemolymph.2019

    • Author(s)
      Ryuno, H., Nigo, F., Naguro, I., Sekimizu, K., and Kaito, C.
    • Journal Title

      PLoS ONE

      Volume: 14

    • DOI

      10.1371/journal.pone.0217517

    • NAID

      120006780367

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 浸透圧ストレスに誘導される細胞代謝の変化2021

    • Author(s)
      名黒 功、生澤 孟志
    • Organizer
      第5回メカノバイオロジー学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 細胞競合によるScribble欠損細胞の排除機構の解析2020

    • Author(s)
      小川 基行、名黒 功、一條 秀憲
    • Organizer
      第19回次世代を担う若手のためのファーマ・バイオフォーラム(薬学会)
    • Related Report
      2020 Annual Research Report
  • [Presentation] TRPM4は細胞内液滴の流動性制御を介してASK3不活性化に寄与する2020

    • Author(s)
      森下 和浩、渡邊 謙吾、名黒 功、一條 秀憲
    • Organizer
      第19回次世代を担う若手のためのファーマ・バイオフォーラム(薬学会)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高浸透圧環境におけるストレス応答および 免疫応答に対する新規NFAT5制御分子HES1の機能解析2020

    • Author(s)
      立野 浩輝、名黒 功、一條 秀憲
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高浸透圧ストレスにより起きる 代謝リプログラミングとその生理的意義2020

    • Author(s)
      生澤 孟志、名黒 功、池田 和貴、有田 誠、一條 秀憲
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Signaling mechanisms and physiological roles of osmotic stress response2020

    • Author(s)
      Isao Naguro, Hidenori Ichijo
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Scribble欠損細胞から分泌されるFGF21は細胞競合を誘導する2020

    • Author(s)
      小川 基行、名黒 功、一條 秀憲
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] NFAT5の高浸透圧応答性を促進するHes1の同定2019

    • Author(s)
      名黒功、立野浩輝、一條秀憲
    • Organizer
      第19回日本蛋白質科学会年会、第71回日本細胞生物学会大会 合同年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 哺乳類細胞における浸透圧ストレスシグナリングの解明とその役割2019

    • Author(s)
      名黒功、一條秀憲
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 相分離が高浸透圧ストレス下でのPP6によるASK3不活性化を制御する2019

    • Author(s)
      渡邊謙吾、名黒功、一條秀憲
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高浸透圧環境におけるストレス応答および免疫応答に対する新規NFAT5制御分子HES1の機能解析2019

    • Author(s)
      立野浩輝、名黒功、一條秀憲
    • Organizer
      第14回日本臨床ストレス応答学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高浸透圧環境におけるストレス応答および免疫応答に対する新規NFAT5制御分子HES1の機能解析2019

    • Author(s)
      立野浩輝、名黒功、一條秀憲
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アセトアミノフェン誘導性肝障害 (AILF) におけるストレス応答キナーゼASK3の機能解析2019

    • Author(s)
      関口雅子、名黒功、一條秀憲
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高浸透圧ストレスは細胞のミトコンドリア呼吸に関わる代謝を変化させる2019

    • Author(s)
      生澤孟志、名黒功、池田和貴、有田誠、一條秀憲
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Analysis of HES1 as a Novel Regulator of NFAT5 under Hyper-Osmotic Stress2019

    • Author(s)
      Hiroki Ryuno, Isao Naguro, Hidenori Ichijo
    • Organizer
      FASEB Science Research Conference (The Molecular Mechanisms of Immune Cell Development and Function Conference)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 浸透圧勾配が引き起こす上皮細胞シートのドーム形成2019

    • Author(s)
      石原(石田)すみれ、秋山 正和、古澤 和也、名黒 功、立野 浩輝、須志田 隆道、石原 誠一郎、芳賀 永
    • Organizer
      2018年度日本生物物理学会北海道支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] シングルセルウェスタン法を用いた細胞の浸透圧ストレス応答の解析2019

    • Author(s)
      名黒 功、立野 浩輝
    • Organizer
      第4回メカノバイオロジー学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] NFAT5の高浸透圧応答性を促進するHes1の同定2019

    • Author(s)
      名黒 功、立野 浩輝、一條 秀憲
    • Organizer
      第71回日本細胞生物学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規NFAT5核内移行制御因子HES1の同定と高浸透圧環境における機能2018

    • Author(s)
      立野 浩輝、名黒 功、一條 秀憲
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] プロテアソーム依存的なASK3の不活性化による高浸透圧ストレス応答の制御2018

    • Author(s)
      周 翔宇、渡邊 謙吾、森下 和浩、名黒 功、一條 秀憲
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京大学大学院薬学系研究科 細胞情報学教室

    • URL

      http://www.f.u-tokyo.ac.jp/~toxicol/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東京大学 大学院薬学系研究科 細胞情報学教室

    • URL

      http://www.f.u-tokyo.ac.jp/~toxicol/index.html

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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