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Identification of new myokines based on new hypotheses

Research Project

Project/Area Number 22K19731
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 InstitutionOsaka University

Principal Investigator

Fukada So-ichiro  大阪大学, 大学院薬学研究科, 教授 (20432445)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsマイオカイン / 間葉系前駆細胞 / リモデリング / 筋肥大 / マクロファージ / 運動
Outline of Research at the Start

マイオカインの多くはサイトカインであり,その場合には血液中にごく微量にしか存在しないため,全く新しいマイオカインを同定することは今のタンパク同定手法を駆使してもかなり困難であり多額の費用を要する。一方で,培養上清からの同定や,因子が特定できている場合には微量であっても血液での検出可能である。申請者の独自の成果である,運動と間葉系前駆細胞の研究や,運動負荷依存的に間葉系前駆細胞が発現する因子の情報を元に,間葉系前駆細胞が直接・間接的 にマイオカイン発現に働く仮説をたて,運動依存的に放出される新規マイオカイン同定を目指した検討を行う。

Outline of Final Research Achievements

Based on our original data, we hypothesized that mesenchymal progenitor cells in the muscle stroma are directly or indirectly involved in the production of exercise-dependent myokines. To clarify this hypothesis, we performed experiments using resistance and running, wheel running, genetically modified animals and RNA-seq analysis. The results revealed that Ccl2 and Ccl7, which are involved in monocyte recruitment, are mainly expressed by mesenchymal progenitor cells. Further we attempted to identify novel myokines, but the resistance training model failed to identify confident factors. However, we found that a significant contribution of mesenchymal progenitor cells to the expression of the extracellular matrix, a component of muscle remodelling.

Academic Significance and Societal Importance of the Research Achievements

運動依存的に発現するマイオカイン研究は,世界中で注目をあつめている研究領域の1つである。CCL2は運動により増加するケモカインかつマイオカインであるが,筋の間葉系前駆細胞が主として分泌している結果は,これまで筋線維のみに焦点があたっていたマイオカイン研究に,一石を投じる成果であり,この研究領域の発展につながることが期待される。運動は唯一の安全で効果的なアンチエイジング法であり,その一助はマイオカインに依存していると言われている。本研究の成果を元に,運動のマイオカインを介した生命現象の解明は,人類の夢である健康長寿につながる可能性が期待される。

Report

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

    (10 results)

All 2024 2023 2022

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [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] Pdgfrα+ stromal cells, a key regulator for tissue homeostasis and dysfunction in distinct organs2024

    • Author(s)
      Kang X, Zhao K, Huang Z, Fukada SI*, Gi X*, Miao H*
    • Journal Title

      Genes & Diseases

      Volume: in press

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Flow Cytometer Analyses, Isolation, and Staining of Murine Muscle Satellite Cells2023

    • Author(s)
      Kubota M, Zhang L, Fukada SI.
    • Journal Title

      Methods Mol Biol.

      Volume: 26 Pages: 3-11

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles and heterogeneity of mesenchymal progenitors in muscle homeostasis, hypertrophy, and disease.2023

    • Author(s)
      Fukada SI, Uezumi A.
    • Journal Title

      Stem Cells

      Volume: in press

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Whole-mount immunofluorescence staining of mesenchymal progenitors in murine plantaris muscle2022

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

      STAR Protoc

      Volume: 3 Pages: 101593-101593

    • 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 A, Kaji T, Saito H, Higashimoto T, Nakamura A, Kurosawa T, Ikemoto-Uezumi M, Uezumi A, Fukada SI.
    • Journal Title

      STAR Protoc

      Volume: 3 Pages: 101307-101307

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differences in muscle satellite cell dynamics during muscle hypertrophy and regeneration2022

    • Author(s)
      Fukada SI, Higashimoto T, Kaneshige A.
    • Journal Title

      Skelet Muscle

      Volume: 12 Pages: 17-17

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Distinctive and decisive functions of muscle stem cells and mesenchymal progenitors in skeletal muscle regeneration and hypertrophy2023

    • Author(s)
      So-ichiro Fukada
    • Organizer
      JAPAN Bone Academy
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨格筋の再生・肥大機構2022

    • Author(s)
      深田宗一朗
    • Organizer
      第45回日本分子生物学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 骨格筋のストレス応答: 力学的負荷への骨格筋内の細胞応答2022

    • Author(s)
      深田宗一朗
    • Organizer
      第8回日本筋学会学術集会
    • Related Report
      2022 Research-status Report
    • Invited

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Published: 2022-07-05   Modified: 2025-01-30  

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