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Novel regulatory mechanism of skeletal muscle mass via protein methylation

Research Project

Project/Area Number 20K07315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionFujita Health University

Principal Investigator

Hitachi Keisuke  藤田医科大学, 医科学研究センター, 講師 (10508469)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsメチル化修飾 / 骨格筋 / 筋疾患 / 筋萎縮 / メチル化酵素 / 翻訳後修飾 / 筋機能
Outline of Research at the Start

骨格筋量の減少(筋萎縮)は、健康寿命の延伸を妨げる主要因である。申請者はこれまでに、タンパク質の翻訳後修飾の一つであるメチル化修飾の変化が骨格筋量に影響を与えることを見出している。しかしながら、タンパク質のメチル化修飾がどのような分子経路で筋量を制御しているのかは未だ不明である。本研究では、骨格筋におけるタンパク質のメチル化修飾の消失が筋萎縮を引き起こす分子機構を遺伝子改変マウスを用いて明らかにし、ヒトの筋萎縮に対する新たな治療法を確立することを目指す。

Outline of Final Research Achievements

I have investigated the role of Mettl21e in regulating skeletal muscle mass by analyzing knockout mice of Mettl21e and knock-in mice of its target protein. Through this study, I have successfully elucidated the molecular mechanism underlying the methylation by Mettl21e. Additionally, my focus on Mettl21e has allowed me to shed light on the previously unclear relationship between methylation and human muscle disorders. Furthermore, during the generation of knock-in mice, I obtained double knockout mice of myosin. The analysis of these mice has revealed a potential association between fast-twitch myosin and human muscle disorder.

Academic Significance and Societal Importance of the Research Achievements

Mettl21eによるタンパク質のメチル化修飾を介した骨格筋量の制御メカニズムは、従来のタンパク質分解・合成の枠に囚われない新たな筋量制御機構である可能性を見出すことができた。また、ヒト筋疾患サンプルにおいてもメチル化修飾が変化していることが見出せた。よって本研究により、タンパク質のメチル化修飾を基軸とすることでヒトの筋萎縮・筋疾患に対する新たな治療戦略を構築することが可能になると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Simultaneous loss of skeletal muscle myosin heavy chain <scp>IIx</scp> and <scp>IIb</scp> causes severe skeletal muscle hypoplasia in postnatal mice2022

    • Author(s)
      Hitachi Keisuke、Kiyofuji Yuri、Yamaguchi Hisateru、Nakatani Masashi、Inui Masafumi、Tsuchida Kunihiro
    • Journal Title

      The FASEB Journal

      Volume: 37 Issue: 1

    • DOI

      10.1096/fj.202200581r

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Functional Role of Long Non-Coding RNA in Myogenesis and Skeletal Muscle Atrophy2022

    • Author(s)
      Hitachi Keisuke、Honda Masahiko、Tsuchida Kunihiro
    • Journal Title

      Cells

      Volume: 11 Issue: 15 Pages: 2291-2291

    • DOI

      10.3390/cells11152291

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Myostatin Inhibitory d-Peptides to Enhance the Potency, Increasing Skeletal Muscle Mass in Mice2022

    • Author(s)
      Takayama Kentaro、Hitachi Keisuke、Okamoto Hideyuki、Saitoh Mariko、Odagiri Miki、Ohfusa Rina、Shimada Takahiro、Taguchi Akihiro、Taniguchi Atsuhiko、Tsuchida Kunihiro、Hayashi Yoshio
    • Journal Title

      ACS Medicinal Chemistry Letters

      Volume: 13 Issue: 3 Pages: 492-498

    • DOI

      10.1021/acsmedchemlett.1c00705

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Myoparr-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation2021

    • Author(s)
      Hitachi Keisuke、Kiyofuji Yuri、Nakatani Masashi、Tsuchida Kunihiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 1 Pages: 108-108

    • DOI

      10.3390/ijms23010108

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomic and Biological Analyses Reveal the Effect on Growth under Flooding Stress of Chickpea Irradiated with Millimeter Waves2021

    • Author(s)
      Komatsu Setsuko、Maruyama Junya、Furuya Takashi、Yin Xiaojian、Yamaguchi Hisateru、Hitachi Keisuke、Miyashita Natsuki、Tsuchida Kunihiro、Tani Masahiko
    • Journal Title

      Journal of Proteome Research

      Volume: 20 Issue: 10 Pages: 4718-4727

    • DOI

      10.1021/acs.jproteome.1c00368

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proteomic and Biochemical Analyses of the Mechanism of Tolerance in Mutant Soybean Responding to Flooding Stress2021

    • Author(s)
      Komatsu Setsuko、Yamaguchi Hisateru、Hitachi Keisuke、Tsuchida Kunihiro、Kono Yuhi、Nishimura Minoru
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 16 Pages: 9046-9046

    • DOI

      10.3390/ijms22169046

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy2021

    • Author(s)
      Hitachi Keisuke、Nakatani Masashi、Kiyofuji Yuri、Inagaki Hidehito、Kurahashi Hiroki、Tsuchida Kunihiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 5 Pages: 2558-2558

    • DOI

      10.3390/ijms22052558

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osmotic stress in banana is relieved by exogenous nitric oxide2021

    • Author(s)
      Mohd Amnan Muhammad Asyraf、Pua Teen-Lee、Lau Su-Ee、Tan Boon Chin、Yamaguchi Hisateru、Hitachi Keisuke、Tsuchida Kunihiro、Komatsu Setsuko
    • Journal Title

      PeerJ

      Volume: 9 Pages: e10879-e10879

    • DOI

      10.7717/peerj.10879

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Optimized Protein Extraction Method for Gel-Free Proteomic Analysis of Opuntia Ficus-Indica2021

    • Author(s)
      Hashiguchi Akiko、Yamaguchi Hisateru、Hitachi Keisuke、Watanabe Kazuo
    • Journal Title

      Plants

      Volume: 10 Issue: 1 Pages: 115-115

    • DOI

      10.3390/plants10010115

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Effect of Mung Bean (Vigna radiata (L.)) Coat Extract on Mouse Liver Metabolism During Progesterone Withdrawal2020

    • Author(s)
      Hashiguchi Akiko、Okabayashi Koji、Yamaguchi Hisateru、Tsuchida Kunihiro、Hitachi Keisuke、Isoda Hiroko
    • Journal Title

      Journal of Medicinal Food

      Volume: 23 Issue: 9 Pages: 967-977

    • DOI

      10.1089/jmf.2020.4703

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A comparative proteomic analysis of engineered and bio synthesized silver nanoparticles on soybean seedlings2020

    • Author(s)
      Mustafa Ghazala、Hasan Murtaza、Yamaguchi Hisateru、Hitachi Keisuke、Tsuchida Kunihiro、Komatsu Setsuko
    • Journal Title

      Journal of Proteomics

      Volume: 224 Pages: 103833-103833

    • DOI

      10.1016/j.jprot.2020.103833

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 複数の速筋型ミオシン重鎖の同時欠損は重度の筋萎縮を引き起こす2023

    • Author(s)
      常陸圭介, 清藤友梨, 山口央輝, 中谷直史, 乾雅史, 土田邦博
    • Organizer
      日本動物学会関東支部第75回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] タンパク質メチル化修飾を介した速筋型ミオシン重鎖活性の制御2022

    • Author(s)
      常陸圭介, 山口央輝, 清藤友梨, 中谷直史, 乾雅史, 小澤龍彦, 茅元司, 土田邦博
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] The functional role of long non-coding RNAs (lncRNAs) in skeletal muscle atrophy2022

    • Author(s)
      Keisuke Hitachi, Kunihiro Tsuchida
    • Organizer
      The 8th Asian Conference for Frailty and Sarcopenia
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エクソーム解析による筋損傷・筋疾患の原因となる新たな遺伝子変異の同定2022

    • Author(s)
      伊藤祐太朗, 常陸圭介, 土田邦博
    • Organizer
      第69回中部日本生理学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Myh1とMyh4遺伝子の同時欠損による骨格筋機能への影響の解析2022

    • Author(s)
      常陸圭介, 清藤友梨, 山口央輝, 中谷直史, 乾雅史, 土田邦博
    • Organizer
      第8回日本筋学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 長鎖非コードRNAによる骨格筋量の調節機構2021

    • Author(s)
      常陸圭介, 土田邦博
    • Organizer
      第76回日本体力医学会大会 シンポジウム 卓越研究員企画:若手研究者による骨格筋の分子生物学 -基礎から臨床まで-
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Identification and characterization of novel long non-coding RNAs associated with multiple skeletal muscle atrophy2021

    • Author(s)
      Keisuke Hitachi, Kunihiro Tsuchida
    • Organizer
      Noncoding RNA World: From Mechanism to Therapy
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 複数の骨格筋萎縮モデルを用いた新規長鎖非コードRNAの発現変化の解析2020

    • Author(s)
      常陸圭介、土田邦博
    • Organizer
      第6回日本筋学学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] タンパク質メチル化修飾を介した新たな骨格筋量調節機構の解析2020

    • Author(s)
      常陸圭介、山口央輝、中谷直史、乾雅史、土田邦博
    • Organizer
      第43回日本分子生物学会年会ワークショップ
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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