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Novel mechanisms by which skeletal muscle senses exercise stimuli

Research Project

Project/Area Number 21K19753
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionKyushu University (2022-2023)
The University of Tokushima (2021)

Principal Investigator

Uezumi Akiyoshi  九州大学, 生体防御医学研究所, 教授 (60434594)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords骨格筋 / 運動 / 間葉系前駆細胞
Outline of Research at the Start

骨格筋による運動刺激の感知機構は不明な点が多い。最近、運動による筋の代謝リプログラミングに2型自然リンパ球(ILC2)から産生されるIL-13が必要であることが示された。IL-33はILC2の誘導に必要なサイトカインであるが、申請者らは独自に発見した間葉系前駆細胞がIL-33を特異的に発現すること、そして、その発現が運動によって増加することを見出している。運動-間葉系前駆細胞-IL-33-ILC2-IL-13から成る筋代謝リプログラミングカスケードが示唆される。本研究では、「運動-間葉系前駆細胞-IL-33」経路(運動感知経路)について精査し、筋の適応のトリガーとなる機構の解明を目指す。

Outline of Final Research Achievements

One of the most common physical adaptations of exercise is the improvement of skeletal muscle function. The beneficial effects of exercise on skeletal muscle are not only known experientially, but have also been proven scientifically. However, the mechanisms that sense exercise stimuli and trigger skeletal muscle adaptation, in other words, the most upstream events directly affected by exercise, remain enigmatic. Until now, muscle fibres have been the research focus when studying the mechanisms of exercise-induced muscle adaptation. Skeletal muscle tissue, on the other hand, contains many non-muscle cells in addition to muscle fibres, of which mesenchymal progenitors are considered to be particularly important. The present study aimed to clarify the role of mesenchymal progenitors in exercise-induced muscle adaptation.

Academic Significance and Societal Importance of the Research Achievements

運動が身体に様々な有益効果をもたらすことは、経験的に知られているだけでなく、科学的にも立証されている。しかし、運動が直接的に影響する最も上流の部分は謎に包まれてきた。本研究では、運動による機械刺激を間葉系前駆細胞が感知し、骨格筋の強化・適応を誘導するメカニズムを明らかにした。本研究の成果は、効果的な運動療法や、運動模倣薬の開発に資する情報を提供し、サルコペニアやフレイルといった老年症候群に対する効果的な解決策の立案につながると期待できる。

Report

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

    (19 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (8 results) (of which Invited: 8 results)

  • [Int'l Joint Research] Max Planck Institute(ドイツ)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Regulation of muscle hypertrophy through granulin: Relayed communication among mesenchymal progenitors, macrophages, and satellite cells2024

    • Author(s)
      Zhang Lidan、Saito Hayato、Higashimoto Tatsuyoshi、Kaji Takayuki、Nakamura Ayasa、Iwamori Kanako、Nagano Ryoko、Motooka Daisuke、Okuzaki Daisuke、Uezumi Akiyoshi、Seno Shigeto、Fukada So-ichiro
    • Journal Title

      Cell Reports

      Volume: 43 Issue: 4 Pages: 114052-114052

    • DOI

      10.1016/j.celrep.2024.114052

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analyses of Mesenchymal Progenitors in Skeletal Muscle by Fluorescence-Activated Cell Sorting and Tissue Clearing2023

    • Author(s)
      Ikemoto-Uezumi M, Kurosawa T, Minato K, Uezumi A
    • Journal Title

      Methods Mol Biol

      Volume: 2640 Pages: 117-127

    • DOI

      10.1007/978-1-0716-3036-5_9

    • ISBN
      9781071630358, 9781071630365
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Depletion of CD206+ M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration2022

    • Author(s)
      Nawaz Allah et al.
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 7058-7058

    • DOI

      10.1038/s41467-022-34191-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Whole-mount immunofluorescence staining of mesenchymal progenitors in murine plantaris muscle.2022

    • Author(s)
      Kurosawa T, Ikemoto-Uezumi M, Kaneshige A, Fukada S, Uezumi A
    • Journal Title

      STAR Protocols

      Volume: 3(3) Issue: 3 Pages: 101593-101593

    • DOI

      10.1016/j.xpro.2022.101593

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of muscle stem cell-derived myonuclei in murine overloaded muscles2022

    • Author(s)
      Kaneshige Akihiro、Kaji Takayuki、Saito Hayato、Higashimoto Tatsuyoshi、Nakamura Ayasa、Kurosawa Tamaki、Ikemoto-Uezumi Madoka、Uezumi Akiyoshi、Fukada So-ichiro
    • Journal Title

      STAR Protocols

      Volume: 3 Issue: 2 Pages: 101307-101307

    • DOI

      10.1016/j.xpro.2022.101307

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation2022

    • Author(s)
      Yoshimoto Yuki、Uezumi Akiyoshi、Ikemoto-Uezumi Madoka、Tanaka Kaori、Yu Xinyi、Kurosawa Tamaki、Yambe Shinsei、Maehara Kazumitsu、Ohkawa Yasuyuki、Sotomaru Yusuke、Shukunami Chisa
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 780038-780038

    • DOI

      10.3389/fcell.2022.780038

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased MFG‐E8 at neuromuscular junctions is an exacerbating factor for sarcopenia‐associated denervation2021

    • Author(s)
      Ikemoto‐Uezumi Madoka、Zhou Heying、Kurosawa Tamaki、Yoshimoto Yuki、Toyoda Masashi、Kanazawa Nobuo、Nakazawa Tatsu、Morita Mitsuhiro、Tsuchida Kunihiro、Uezumi Akiyoshi
    • Journal Title

      Aging Cell

      Volume: 21 Issue: 1 Pages: 1-15

    • DOI

      10.1111/acel.13536

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load.2021

    • Author(s)
      Kaneshige A, Kaji T, Zhang L, Saito H, Nakamura A, Kurosawa T, Ikemoto-Uezumi M, Tsujikawa K, Seno S, Hori M, Saito Y, Matozaki T, Maehara K, Ohkawa Y, Potente M, Watanabe S, Braun T, Uezumi A, Fukada SI.
    • Journal Title

      Cell Stem Cell.

      Volume: 29 Issue: 2 Pages: 265-280

    • DOI

      10.1016/j.stem.2021.11.003

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Measurement of Lateral Transmission of Force in the Extensor Digitorum Longus Muscle of Young and Old Mice2021

    • Author(s)
      Minato K, Yoshimoto Y, Kurosawa T, Watanabe K, Kawashima H, Ikemoto-Uezumi M, Uezumi A
    • Journal Title

      Int J Mol Sci

      Volume: 22 Issue: 22 Pages: 12356-12356

    • DOI

      10.3390/ijms222212356

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transgenic Expression of Bmp3b in Mesenchymal Progenitors Mitigates Age-Related Muscle Mass Loss and Neuromuscular Junction Degeneration2021

    • Author(s)
      Kurosawa Tamaki、Minato Keitaro、Ikemoto-Uezumi Madoka、Hino Jun、Tsuchida Kunihiro、Uezumi Akiyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10246-10246

    • DOI

      10.3390/ijms221910246

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 間葉系間質細胞の不均一性が支える骨格筋維持メカニズム2023

    • Author(s)
      上住 聡芳
    • Organizer
      第71回 日本職業・災害医学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 筋間質の間葉系前駆細胞とサルコペニアの関わり2022

    • Author(s)
      上住 聡芳
    • Organizer
      第10回日本運動器理学療法学会学術大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 間質の間葉系前駆細胞による筋の維持・適応機構2022

    • Author(s)
      上住 聡芳
    • Organizer
      第69回日本実験動物学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 再生と炎症の収束をカップリングする間葉系細胞の新機能2021

    • Author(s)
      上住 聡芳
    • Organizer
      第7回日本筋学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 間質の間葉系前駆細胞による筋の維持メカニズム2021

    • Author(s)
      上住 聡芳
    • Organizer
      第39回日本骨代謝学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 運動依存性の筋線維由来因子の同定と機能解析2021

    • Author(s)
      上住 聡芳
    • Organizer
      第23回日本骨粗鬆症学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 間質の間葉系前駆細胞による骨格筋の維持機構2021

    • Author(s)
      上住 聡芳
    • Organizer
      第53回日本結合組織学会学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 筋間質の間葉系前駆細胞の老化によるサルコペニアの発症機序2021

    • Author(s)
      上住 聡芳
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
    • Invited

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Published: 2021-07-13   Modified: 2025-01-30  

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