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Molecular Cell Biology of Fatigue Mechanisms Approached from Developmental Studies of Cellular Stress and Inflammation

Research Project

Project/Area Number 21H03334
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59020:Sports sciences-related
Research InstitutionKanazawa Medical University

Principal Investigator

IWAWAKI Takao  金沢医科大学, 総合医学研究所, 教授 (50342754)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords疲労 / 睡眠 / 運動 / 細胞ストレス / 炎症 / ストレス
Outline of Research at the Start

疲労のナゾに迫る研究を行う。疲労は発熱や痛みと共に生体3大アラームと言われ、私たちの生命や健康を維持する上でカラダが発する重要なシグナルであるが、その研究と理解は発熱や痛みに比べて遅れており、科学が進んだ現代でも疲労の実態は掴めていない。本研究では初めに疲労研究のためのマウス実験系を構築する。次に生体イメージングとオミックス解析から細胞ストレスや炎症が疲労の発生/回復に関与する可能性を検証し、最終的には疲労のメカニズムを分子/細胞レベルで解明する。疲労に苦しむ人々は非常に多く、これは現代社会において決して無視できない大きな問題であり、その解決の新たな糸口となることを目指して本研究に取り組む。

Outline of Final Research Achievements

Fatigue, along with fever and pain, is one of the three major biological alarms, and is an important signal given by the body to maintain life and health. However, research and understanding of fatigue has lagged behind that of fever and pain, and even in today's advanced scientific age, the actual state of fatigue is not well understood. The principal investigator has been involved in research on cellular stress and inflammation in experimental systems using mice, and has come to the hypothesis that these factors are involved in fatigue. In this study, we first established a mouse experimental system for fatigue research. Next, we are elucidating the possibility that cellular stress and inflammation are involved in the generation/recovery of fatigue based on in vivo imaging analysis.

Academic Significance and Societal Importance of the Research Achievements

疲労に苦しむ人々は非常に多く、これは現代社会において決して無視できない大きな問題であり、その解決の新たな糸口となることを目指して本研究に取り組んだ。特に重要なのは、この研究から明らかになることが単に基礎的な生命科学へ貢献するだけでなく、疲労が生む社会問題(健康障害から事故・自殺に至るまで)の解決へ繋がる可能性を十分に含んでいることである。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (51 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (11 results) Journal Article (18 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 18 results,  Open Access: 14 results) Presentation (22 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Int'l Joint Research] コーネル大学/UCSF(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] マクギル大学(カナダ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] チリ大学(チリ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 江原大学校(韓国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of North Carolina/Weill Cornell Medicine(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Bordeaux University/C3M(フランス)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Sanquin(オランダ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] ヒューストン大学/コロラド大学/UCSF(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] マギル大学(カナダ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] 全北大学校(韓国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] キュリー研究所(フランス)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Partial limitation of cellular functions and compensatory modulation of unfolded protein response pathways caused by double-knockout of ATF6α and ATF6β2024

    • Author(s)
      Akai R, Hamashima H, Saito M, Kohno K, Iwawaki T
    • Journal Title

      Cell Stress Chaperones

      Volume: 29 Issue: 1 Pages: 34-48

    • DOI

      10.1016/j.cstres.2023.11.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic change and preventive role of stress response via Keap1-Nrf2 during renal crystal formation2023

    • Author(s)
      Ushimoto C, Sugiki S, Kunii K, Inoue S, Kuroda E, Akai R, Iwawaki T, Miyazawa K
    • Journal Title

      Free Radic Biol Med

      Volume: 207 Pages: 120-132

    • DOI

      10.1016/j.freeradbiomed.2023.07.013

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammatory ER stress responses dictate the immunopathogenic progression of systemic candidiasis2023

    • Author(s)
      Awasthi D, Chopra S, Cho BA, Emmanuelli A, Sandoval TA, Hwang SM, Chae CS, Salvagno C, Tan C, Vasquez-Urbina L, Fernandez Rodriguez JJ, Santagostino SF, Iwawaki T, Romero-Sandoval EA, Crespo MS, Morales DK, Iliev ID, Hohl TM, Cubillos-Ruiz JR
    • Journal Title

      J Clin Invest

      Volume: 133 Issue: 17

    • DOI

      10.1172/jci167359

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Unfolded Protein Response Sensor IRE1 Regulates Activation of In Vitro Differentiated Type 1 Conventional DCs with Viral Stimuli2023

    • Author(s)
      Medel B, Bernales JI, Lira A, Fernandez D, Iwawaki T, Vargas P, Osorio F
    • Journal Title

      Int J Mol Sci

      Volume: 24 Issue: 12 Pages: 10205-10205

    • DOI

      10.3390/ijms241210205

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity2023

    • Author(s)
      Flores-Santibanez F, Rennen S, Fernandez D, De Nolf C, Van De Velde E, Gaete Gonzalez S, Fuentes C, Moreno C, Figueroa D, Lladser A, Iwawaki T, Bono MR, Janssens S, Osorio F
    • Journal Title

      Front Immunol

      Volume: 14 Pages: 1209588-1209588

    • DOI

      10.3389/fimmu.2023.1209588

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deletion of the Unfolded Protein Response Transducer IRE1α Is Detrimental to Aging Photoreceptors and to ER Stress-Mediated Retinal Degeneration2023

    • Author(s)
      Massoudi D, Gorman S, Kuo YM, Iwawaki T, Oakes SA, Papa FR, Gould DB
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 64 Issue: 4 Pages: 30-30

    • DOI

      10.1167/iovs.64.4.30

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions2023

    • Author(s)
      Jeong H, Hong EH, Ahn JH, Cho J, Jeong JH, Kim CW, Yoon BI, Koo JH, Park YY, Yang YM, Iwawaki T, Vallance BA, Chang SY, Ko HJ
    • Journal Title

      Exp Mol Med

      Volume: 55 Issue: 2 Pages: 401-412

    • DOI

      10.1038/s12276-023-00945-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alterations in UPR Signaling by Methylmercury Trigger Neuronal Cell Death in the Mouse Brain2022

    • Author(s)
      Nomura Ryosuke、Takasugi Nobumasa、Hiraoka Hideki、Iijima Yuta、Iwawaki Takao、Kumagai Yoshito、Fujimura Masatake、Uehara Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 23 Pages: 15412-15412

    • DOI

      10.3390/ijms232315412

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Salmonella Exhibit Altered Cellular Localization in the Presence of HLA-B27 and Codistribute with Endo-Reticular Membrane2022

    • Author(s)
      Kriston-Vizi Janos、Lenart Izabela、Iwawaki Takao、Gould Keith、Nesbeth Darren、Powis Simon J.、Antoniou Antony N.
    • Journal Title

      Journal of Immunology Research

      Volume: 2022 Pages: 9493019-9493019

    • DOI

      10.1155/2022/9493019

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The unfolded protein response transducer IRE1α promotes reticulophagy in podocytes2022

    • Author(s)
      Navarro-Betancourt Jos? R.、Papillon Joan、Guillemette Julie、Chung Chen-Fang、Iwawaki Takao、Cybulsky Andrey V.
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1868 Issue: 6 Pages: 166391-166391

    • DOI

      10.1016/j.bbadis.2022.166391

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intercepting IRE1 kinase‐FMRP signaling prevents atherosclerosis progression2022

    • Author(s)
      Yildirim Zehra、Baboo Sabyasachi、Hamid Syed M、Dogan Asli E、Tufanli Ozlem、Robichaud Sabrina、Emerton Christina、Diedrich Jolene K、Vatandaslar Hasan、Nikolos Fotis、Gu Yanghong、Iwawaki Takao、Tarling Elizabeth、Ouimet Mireille、Nelson David L、Yates John R、Walter Peter、Erbay Ebru
    • Journal Title

      EMBO Molecular Medicine

      Volume: 14 Issue: 4

    • DOI

      10.15252/emmm.202115344

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Targeting IRE1 endoribonuclease activity alleviates cardiovascular lesions in a murine model of Kawasaki disease vasculitis2022

    • Author(s)
      Marek-Iannucci Stefanie、Yildirim Asli D.、Hamid Syed M.、Ozdemir Asli B.、Gomez Angela C.、Kocat?rk Beg?m、Porritt Rebecca A.、Fishbein Michael C.、Iwawaki Takao、Noval Rivas Magali、Erbay Ebru、Arditi Moshe
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 6

    • DOI

      10.1172/jci.insight.157203

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 12022

    • Author(s)
      Liu Xiaoying、Taylor Sarah A.、Gromer Kyle D.、Zhang Danny、Hubchak Susan C.、LeCuyer Brian E.、Iwawaki Takao、Shi Zengdun、Rockey Don C.、Green Richard M.
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 1 Pages: e0261789-e0261789

    • DOI

      10.1371/journal.pone.0261789

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 疲労を考える上で関心を向けざるを得ない細胞ストレス応答の分子メカニズム2022

    • Author(s)
      黒田絵莉子, 赤井良子, 岩脇隆夫
    • Journal Title

      日本疲労学会誌

      Volume: 16 Pages: 9-15

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism2021

    • Author(s)
      Roy A, Tomaz da Silva M, Bhat R, Bohnert KR, Iwawaki T, Kumar A
    • Journal Title

      Elife

      Volume: 10

    • DOI

      10.7554/elife.73215

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress2021

    • Author(s)
      Baral H, Sekiguchi A, Uchiyama A, Nisaa Amalia S, Yamazaki S, Inoue Y, Yokoyama Y, Ogino S, Torii R, Hosoi M, Akai R, Iwawaki T, Ishikawa O, Motegi SI
    • Journal Title

      J Dermatol Sci

      Volume: 48 Issue: 7 Pages: 1052-1061

    • DOI

      10.1111/1346-8138.15888

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte-specific deletion of XBP1 sensitizes mice to liver injury through hyperactivation of IRE1α2021

    • Author(s)
      Duwaerts CC, Siao K, Soon RK Jr, Her C, Iwawaki T, Kohno K, Mattis AN, Maher JJ
    • Journal Title

      Cell Death Differ

      Volume: 28 Issue: 5 Pages: 1455-1465

    • DOI

      10.1038/s41418-020-00671-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Spatiotemporal analysis of the UPR transition induced by methylmercury in the mouse brain.2021

    • Author(s)
      Hiraoka, H., Nomura, R., Takasugi, N., Akai, R., Iwawaki, T., Kumagai, Y., Fujimura, M., and Uehara, T.
    • Journal Title

      Arch. Toxicol.

      Volume: 95 Issue: 4 Pages: 1241-1250

    • DOI

      10.1007/s00204-021-02982-9

    • NAID

      120007185542

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ATF6β欠損マウスが示す多動表現型と横隔膜ヘルニア2023

    • Author(s)
      赤井良子、濱嶋尚代、岩脇隆夫
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Deletion of IRE1α Exacerbates Diabetic Nephropathy in Mice2023

    • Author(s)
      Andrey V. Cybulsky, Joan Papillon, Julie Guillemette, Jose R. Navarro-Betancourt, Chen-Fang Chung, Takao Iwawaki, Ivan G. Fantus
    • Organizer
      KIDNEY WEEK 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酸化ストレスの視点から尿路結石学と向き合う2023

    • Author(s)
      牛本千春子、國井建司郎、井上慎也、赤井良子、黒田絵莉子、岩脇隆夫、宮澤克人
    • Organizer
      日本尿路結石症学会第33回学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 運動後急性腎不全の機序解明2023

    • Author(s)
      野村和利、赤井良子、谷田守、矢部友久、熊野奨、宮竹敦彦、岡田圭一郎、大串勇気、沖野一晃、藤 本圭司、倉田康孝、岩脇隆夫、横山仁、古市賢吾
    • Organizer
      第66回日本腎臓学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 酸化ストレスの視点から尿路結石学と向き合う2023

    • Author(s)
      牛本千春子、國井建司郎、井上慎也、赤井良子、黒田絵莉子、岩脇隆夫、宮澤克人
    • Organizer
      第110回日本泌尿器科学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 腎結晶形成におけるKeap1-Nrf2 経路を介したストレス応答の関与2023

    • Author(s)
      牛本千春子、杉木滋、國井建司郎、井上慎也、赤井良子、黒田絵莉子、岩脇隆夫、宮澤克人
    • Organizer
      第26回北陸泌尿器科Research Meeting
    • Related Report
      2023 Annual Research Report
  • [Presentation] ATF6αとATF6βの二重欠損が引き起こすUPR制御機構の代償的変調と細胞機能の関係2022

    • Author(s)
      赤井良子、濱嶋尚代、斉藤美知子、河野憲二、岩脇隆夫
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ATF6αとATF6βの二重欠損が引き起こすUPR制御機構の代償的変調と細胞機能の関係2022

    • Author(s)
      赤井良子、黒田絵莉子、濱嶋尚代、斉藤美知子、河野憲二、岩脇隆夫
    • Organizer
      第16回臨床ストレス応答学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腎結晶形成におけるKeap1-Nrf2経路を介したストレス応答の果たす役割2022

    • Author(s)
      牛本千春子、國井建司郎、井上慎也、赤井良子、黒田絵莉子、岩脇隆夫、宮澤克人
    • Organizer
      第16回臨床ストレス応答学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腎結晶形成におけるKeap1-Nrf2経路を介したストレス応答の関与2022

    • Author(s)
      牛本千春子、國井建司郎、井上慎也、赤井良子、黒田絵莉子、岩脇隆夫、宮澤克人
    • Organizer
      第32回日本尿路結石症学会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 小胞体ストレス応答のシグナル経路により制御される過食行動の分子メカニズム2022

    • Author(s)
      赤井良子、黒田絵莉子、濱嶋尚代、岩脇隆夫
    • Organizer
      第69回日本実験動物学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腎結晶形成における Keap1-Nrf2経路を介した ストレス応答の解析2022

    • Author(s)
      牛本千春子、國井建司郎、井上慎也、黒田絵莉子、赤井良子、岩脇隆夫、宮澤克人
    • Organizer
      第31回泌尿器科分子・細胞研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] Proteostatic sensor Ire1, promotes bone formation by potentiating Wnt signaling in osteoblast progenitors2022

    • Author(s)
      Lakshmi Divya Kolora, Christian Melendez-Suchi, Sara Higsley, Veronica Butler, John Lipold, Takao Iwawaki, Maria Almeida, Kartik Shankar, Douglas J Adams, Srividhya Iyer
    • Organizer
      Gordon Research Conference (Bones and Teeth)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Non-canonical Role for IRE1α in Podocyte Endoplasmic Reticulum (ER)-phagy2021

    • Author(s)
      Jose R. Navarro-Betancourt, Joan Papillon, Julie Guillemette, Takao Iwawaki, Andrey V. Cybulsky
    • Organizer
      KIDNEY WEEK 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体イメージングマウスを用いた腎結晶形成における酸化ストレス応答の解析2021

    • Author(s)
      牛本千春子、國井建司郎、井上慎也、赤井良子、岩脇隆夫、宮澤克人
    • Organizer
      第31回日本尿路結石症学会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞ストレス応答の発展的研究から迫る疲労の分子メカニズム2021

    • Author(s)
      岩脇隆夫
    • Organizer
      第17回日本疲労学会総会・学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリア異常を可視化するマウスの作製に向けた新規FRETレポーター遺伝子の開発2021

    • Author(s)
      黒田絵莉子、赤井良子、濱嶋尚代、岩脇隆夫
    • Organizer
      第56回金沢医科大学医学会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ATF4の翻訳活性化機構に赤色蛍光/発光レポーターを応用した統合ストレス可視化モデルマウスの開発2021

    • Author(s)
      赤井良子、黒田絵莉子、濱嶋尚代、岩脇隆夫
    • Organizer
      第73回日本細胞生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The ER sensor, IRE1, promotes bone formation by increasing nuclear localization of β-catenin in osteoprogenitors2021

    • Author(s)
      Srividhya Iyer, Lakshmi Kolora, Christian Melendez-Suchi, Sara Higsley, Veronica Butler, John Lipold, Takao Iwawaki, Maria Almeida, Kartik Shankar, Douglas Adams
    • Organizer
      FASEB SRC The ER Conferences
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 赤色蛍光/発光レポーターにATF4の翻訳活性化機構を応用した統合ストレス可視化モデルマウスの開発2021

    • Author(s)
      赤井良子、黒田絵莉子、濱嶋尚代、岩脇隆夫
    • Organizer
      第68回日本実験動物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ENDOPLASMIC RETICULUM STRESS IS ASSOCIATED WITH CLINICAL FEATURES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE2021

    • Author(s)
      Tetsuo Nakayama, Shiko Kuribayashi, Takao Iwawaki, Junko Hirato, Ryoko Akai, Yasumori Fukai, Hirohito Tanaka, Taku Tomizawa, Yu Hashimoto, Motoyasu Kusano, Toshio Uraoka
    • Organizer
      Digestive Disease Week 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 炎症性腸疾患における小胞体ストレス応答の関与について2021

    • Author(s)
      中山哲雄、栗林志行、岩脇隆夫、平戸純子、深井泰守、富澤琢、橋本悠、田中寛人、草野元康、浦岡俊夫
    • Organizer
      第101回日本消化器内視鏡学会総会
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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