• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of the mechanism of muscle regeneration and repair starting from the expansion of macrophage diversity

Research Project

Project/Area Number 22K19534
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionInstitute of Science Tokyo (2024)
Tokyo Medical and Dental University (2023)
Nippon Medical School (2022)

Principal Investigator

Oishi Yumiiko  東京科学大学, 大学院医歯学総合研究科, 教授 (80435734)

Project Period (FY) 2022-06-30 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2024: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsマクロファージ / 筋再生 / 組織修復
Outline of Research at the Start

本研究では、マクロファージを機能と相互作用の観点から分類し、マクロファージの時空間多様性を軸とした細胞間相互作用が組織炎症を制御し、修復と再生を実行する分子機序を明らかにする。具体的には、1細胞間相互作用の時空間解析、マクロファージが筋衛星細胞や線維芽細胞の活性化を制御する分子機構の解明を通じ、マクロファージの多様性が、細胞間相互作用ネットワークを介して組織炎症を制御し、修復と再生を実現する分子機序を明らかにする。これらの研究を通じ、筋損傷後の再生不全に対する治療・予防策の開発に向けた知識基盤を確立する。

Outline of Final Research Achievements

This study focused on the pathogenic mechanism of age-related loss of muscle mass and strength (sarcopenia), particularly the intercellular network and regulatory mechanisms involved in impaired regeneration and repair after muscle injury. Single-cell RNA-seq analysis revealed that multiple unknown macrophage subtypes accumulate in the regenerating muscle stroma, that macrophages have diverse spatiotemporal and pathology-specific functions, and that they lead tissue repair through interactions with muscle satellite cells and fibroblasts. In this study, we classified macrophages in terms of function and interaction, and elucidated the role of macrophage diversity in the regulation of tissue inflammation and repair/regeneration at the molecular level.

Translated with DeepL.com (free version)

Academic Significance and Societal Importance of the Research Achievements

本研究は、加齢関連疾患の病態理解を深めるとともに、再生医療や炎症制御の新たな研究基盤を提供する。また、サルコペニアをはじめとする加齢関連疾患の治療・予防法の開発に貢献する可能性をもつ。特に、高齢化社会における健康寿命の延伸や生活の質(Quality Of Life)の向上に寄与し、医療費削減や社会的負担の軽減にもつながることが期待される。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (37 results)

All 2025 2024 2023 2022 Other

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 15 results) Book (2 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Macrophage Subpopulation Promotes Skeletal Muscle Regeneration Through <scp>HGF</scp>/<scp>MET</scp> Signaling‐Mediated Skeletal Muscle Stem Cell Proliferation2025

    • Author(s)
      Koike Hiroyuki、Sugimura Miho、Ouchi Rie、Yoshimoto Yuki、Manabe Ichiro、Oishi Yumiko
    • Journal Title

      Aging Cell

      Volume: 10 Issue: 6 Pages: 70042-70042

    • DOI

      10.1111/acel.70042

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evidence for the Involvement of Gene Regulation of Inflammatory Molecules in the Accumulation of Intracellular Cholesterol: The Mechanismof Foam Cell Formation in Atherosclerosis2024

    • Author(s)
      Sukhorukov Vasily N.、Khotina Victoria A.、Borodko Daria D.、Ekta Mariam Bagheri、Oishi Yumiko、Omelchenko Andrey V.、Kolmychkova Kira I.、Nikiforov Nikita G.、Sobenin Igor A.、Orekhov Alexander N.
    • Journal Title

      Current Medicinal Chemistry

      Volume: 31 Issue: 9 Pages: 2174-2174

    • DOI

      10.2174/0109298673286400240206095814

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Differential effects of theasinensins and epigallocatechin-3-O-gallate on phospholipid bilayer structure and liposomal aggregation2024

    • Author(s)
      Narai-Kanayama Asako、Hayakawa Sumio、Yoshino Takayuki、Honda Futa、Matsuda Hiroko、Oishi Yumiko
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1866 Issue: 5 Pages: 184312-184312

    • DOI

      10.1016/j.bbamem.2024.184312

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Editorial: Metabolic regulation of macrophage functions in inflammation2024

    • Author(s)
      Oishi Yumiko、Sohrabi Yahya、Xiao Peng
    • Journal Title

      Frontiers in Immunology

      Volume: 15 Pages: 3389-3389

    • DOI

      10.3389/fimmu.2024.1369896

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
  • [Journal Article] descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques2024

    • Author(s)
      Otomo Kohei、Omura Takaki、Kaku Masaru、Susaki Etsuo A. et al.
    • Journal Title

      Nature Communications

      Volume: 15 Issue: 1 Pages: 4941-4941

    • DOI

      10.1038/s41467-024-49131-1

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Macrophage SREBP1 regulates skeletal muscle regeneration2024

    • Author(s)
      Oishi Yumiko、Koike Hiroyuki、Kumagami Naoki、Nakagawa Yoshimi、Araki Masaya、Taketomi Yoshitaka、Miki Yoshimi、Matsuda Shigeru、Kim Hyeree、Matsuzaka Takashi、Ozawa Hitoshi、Shimano Hitoshi、Murakami Makoto、Manabe Ichiro
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 1251784-1251784

    • DOI

      10.3389/fimmu.2023.1251784

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristic impairment of progesterone response in cultured cervical fibroblasts obtained from patients with refractory cervical insufficiency2023

    • Author(s)
      Sugita Yosuke、Kuwabara Yoshimitsu、Katayama Akira、Matsuda Shigeru、Manabe Ichiro、Suzuki Shunji、Oishi Yumiko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 11709-11709

    • DOI

      10.1038/s41598-023-37732-7

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arntl deficiency in myeloid cells reduces neutrophil recruitment and delays skeletal muscle repair2023

    • Author(s)
      Watanabe Aiko、Koike Hiroyuki、Kumagami Naoki、Shimba Shigeki、Manabe Ichiro、Oishi Yumiko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 6747-6747

    • DOI

      10.1038/s41598-023-33830-8

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Caspase-4 contributes to Site-1 protease cleavage and SREBP1 activation in the inflammatory response of macrophages.2023

    • Author(s)
      Cheng Y, Manabe I, Hayakawa S, Endo Y, and Oishi Y.
    • Journal Title

      Front Immunol

      Volume: 14 Pages: 1009973-1009973

    • DOI

      10.3389/fimmu.2023.1009973

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] Activated cholesterol metabolism is integral for innate macrophage responses by amplifying Myd88 signaling.2022

    • Author(s)
      Hayakawa S, Tamura A, Nikiforov N, Koike H, Kudo F, Cheng Y, Miyazaki T, Kubekina M, Kirichenko T, Orekhov A, Yui N, Manabe I, Oishi Y.
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 22

    • DOI

      10.1172/jci.insight.138539

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cyclic stretch regulates immune responses via tank-binding kinase 1 expression in macrophages.2022

    • Author(s)
      Nakagawa A, Hayakawa S, Cheng Y, Honda A, Yuzawa R, Ogawa R and Oishi Y.
    • Journal Title

      FEBS Open Bio

      Volume: 10 Issue: 1 Pages: 13626-13626

    • DOI

      10.1002/2211-5463.13526

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms of Cooperative Cell-Cell Interactions in Skeletal Muscle Regeneration.2022

    • Author(s)
      Koike H, Manabe I and Oishi Y.
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1 Pages: 48-48

    • DOI

      10.1186/s41232-022-00234-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol2022

    • Author(s)
      Hayakawa Sumio、Ohishi Tomokazu、Oishi Yumiko、Isemura Mamoru、Miyoshi Noriyuki
    • Journal Title

      Antioxidants

      Volume: 11 Issue: 12 Pages: 2352-2352

    • DOI

      10.3390/antiox11122352

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] マクロファージによる炎症・再生・修復の制御2025

    • Author(s)
      大石由美子
    • Organizer
      第28回アディポサイエンスシンポジウム シンポジウム
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 骨格筋の再生・修復におけるマクロファージの多様性2024

    • Author(s)
      大石由美子
    • Organizer
      CVMW(日本心血管代謝週間)2024
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 脂質代謝からみた慢性子宮内膜炎の病態と治療応用2024

    • Author(s)
      大石由美子
    • Organizer
      第47回 日本分子生物学会年会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] マクロファージの多様性が制御する傷害後の組織修復2024

    • Author(s)
      大石由美子
    • Organizer
      第97回日本生化学会大会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 細胞の多様性と慢性炎症の視点からみる生活習慣病のメカニズム2024

    • Author(s)
      大石由美子
    • Organizer
      基礎研究医プログラム2024年リトリート
    • Related Report
      2024 Annual Research Report
  • [Presentation] Macrophages in muscle repair and regeneration2023

    • Author(s)
      Oishi, Y
    • Organizer
      INSERM-JSPS WORKSHOP “From basic discovery to preclinical modeling: at the forefront of muscle disease therapies”
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of a novel subset of macrophages that regulate muscle repair and regeneration2023

    • Author(s)
      Oishi, Y
    • Organizer
      The 52nd Annual meeting of the Japanese Society of Immunology
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] コレステロールを標的とした新たな動脈硬化治療2023

    • Author(s)
      大石由美子
    • Organizer
      第46回 日本分子生物学会大会 シンポジウム
    • Related Report
      2023 Research-status Report
  • [Presentation] 細胞内脂質代謝によるマクロファージ機能制御2023

    • Author(s)
      大石由美子
    • Organizer
      第96回生化学会大会 シンポジウム
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] 循環器医が基礎研究を行ってダイバーシティを拡げよう2023

    • Author(s)
      大石由美子
    • Organizer
      第27回日本心不全学会学術集会 会長特別企画
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] Identification of a novel subset of macrophages that regulate muscle regeneration2023

    • Author(s)
      大石由美子
    • Organizer
      JSICR/MMCB 2023 合同シンポジウム
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] 筋再生・修復を主導する間質細胞間ネットワーク解析2022

    • Author(s)
      大石由美子
    • Organizer
      第45回日本分子生物学会大会ワークショップ
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 細胞内コレステロールによるマクロファージ機能の制御2022

    • Author(s)
      大石由美子
    • Organizer
      第95回日本生化学会大会 シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Immunometabolism as a novel therapeutic target of atherosclerosis2022

    • Author(s)
      大石由美子
    • Organizer
      第29回 国際高血圧学会ISH2022シンポジウム
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 転写因子KLF5による筋萎縮の制御と新規治療への展開2022

    • Author(s)
      大石由美子
    • Organizer
      第8回筋学会シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] シングルセルトランスクリプトームから読み解く筋再生・修復メカニズム2022

    • Author(s)
      大石由美子
    • Organizer
      第51回 日本心脈管作動物質学会シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 加齢による筋損傷後再生不全のメカニズム2022

    • Author(s)
      大石由美子
    • Organizer
      第64回 日本老年医学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Book] 慢性炎症とサルコペニア 別冊BIOClinica2024

    • Author(s)
      大石由美子
    • Total Pages
      120
    • Publisher
      北隆館、ニューサイエンス社
    • Related Report
      2024 Annual Research Report
  • [Book] 免疫細胞による筋再生制御、医学のあゆみ2024

    • Author(s)
      大石由美子
    • Total Pages
      100
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2024 Annual Research Report
  • [Remarks] 東京科学大学 医歯学総合研究科 病態代謝解析学

    • Related Report
      2024 Annual Research Report
  • [Remarks] 東京医科歯科大学大学院医歯学総合研究科病態代謝解析学

    • URL

      https://www.tmd.ac.jp/mbc/

    • Related Report
      2023 Research-status Report
  • [Remarks] 日本医科大学 代謝・栄養学

    • URL

      https://www.nms.ac.jp/college/schoolroom/kisoigaku/taisya-eiyougaku.html

    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] 慢性子宮内膜炎を治療するための組成物および方法2023

    • Inventor(s)
      大石由美子、松田繁、桑原慶充
    • Industrial Property Rights Holder
      大石由美子、松田繁、桑原慶充
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Research-status Report

URL: 

Published: 2022-07-05   Modified: 2026-01-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi