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Elucidation of the mechanism of muscle catabolism by mononuclear phagocytes

Research Project

Project/Area Number 20K22876
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0902:General internal medicine and related fields
Research InstitutionKagawa University

Principal Investigator

Kitada Kento  香川大学, 医学部, 助教 (30882493)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords食塩 / 筋萎縮 / マクロファージ / 浸透圧 / TonEBP / 筋委縮 / 単核貪食細胞 / 塩 / 体液 / 老化 / 健康寿命
Outline of Research at the Start

加齢や生活習慣病に伴う筋委縮は、生活の質(QOL)および健康寿命の低下に直結するが、その発症・進展機序の詳細は明らかにされておらず、予防・治療法も存在しない。
申請者らは最近、様々な生活習慣病のリスク因子である高食塩摂取が、筋肉の異化反応(カタボリズム)を亢進し、筋肉量の低下を引き起こすことを発見した。しかしながら、高食塩摂取に伴う筋肉量減少メカニズムは不明である。
本研究では、予備検討にて関与が疑われる免疫細胞である単核貪食細胞に焦点を当て、筋肉量減少メカニズムを解明し、加齢や生活習慣病に伴う筋委縮機序の一端を明らかにする。

Outline of Final Research Achievements

We have reported that high salt intake induces muscle protein catabolism and muscle loss in rodents. However, the mechanism of high salt-induced muscle wasting remains to be clarified. In this research project, we focused on the role of mononuclear phagocytes in high salt-induced muscle loss. From the experimental results of this study, we found that the mononuclear phagocytes/TonEBP/protein A pathway plays an important role in salt-driven muscle wasting.

Academic Significance and Societal Importance of the Research Achievements

現代の生活習慣や加齢に伴う筋肉量および筋力の低下(筋委縮)は、生活の質(QOL)や健康寿命を低下させてしまうが、具体的な予防・治療法が存在しないのが現状である。本邦は、食塩摂取量が多い国のひとつであり、高食塩摂取による筋肉のカタボリズム亢進(筋肉量減少)は、加齢や現代の生活習慣に伴う筋委縮メカニズムの一因である可能性が考えられる。本研究により、高食塩摂取に伴う筋萎縮のメカニズムに、単核貪食細胞/TonEBP/蛋白質Aが関与していることが明らかとなった。将来的には本研究の成果を基盤とし、食塩の摂り過ぎや加齢による筋委縮に対する予防・治療法の開発へつなげ、ヒトの健康寿命延長を目指す。

Report

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

    (9 results)

All 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (3 results) (of which Invited: 3 results)

  • [Int'l Joint Research] Duke-NUS Medical School(シンガポール)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Duke-NUS Medical School(シンガポール)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Hepatocellular carcinoma induces body mass loss in parallel with osmolyte and water retention in rats2022

    • Author(s)
      Kidoguchi Satoshi、Kitada Kento、Nakajima Kazuki、Nakano Daisuke、Ohsaki Hiroyuki、Kittikulsuth Wararat、Kobara Hideki、Masaki Tsutomu、Yokoo Takashi、Takahashi Kazuo、Titze Jens、Nishiyama Akira
    • Journal Title

      Life Sciences

      Volume: 289 Pages: 120192-120192

    • DOI

      10.1016/j.lfs.2021.120192

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sodium/glucose cotransporter 2 and renoprotection: From the perspective of energy regulation and water conservation.2021

    • Author(s)
      Kento Kitada, Satoshi Kidoguchi, Daisuke Nakano, Akira Nishiyama.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 147 Issue: 3 Pages: 245-250

    • DOI

      10.1016/j.jphs.2021.07.006

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect2021

    • Author(s)
      Wild Johannes、Kitada Kento、et al.
    • Journal Title

      Acta Physiologica

      Volume: 16 Issue: 1

    • DOI

      10.1111/apha.13628

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adaptive physiological water conservation explains hypertension and muscle catabolism in experimental chronic renal failure2021

    • Author(s)
      Kovarik Johannes J.、Morisawa Norihiko、Wild Johannes、Marton Adriana、Takase‐Minegishi Kaoru、Minegishi Shintaro、Daub Steffen、Sands Jeff M.、Klein Janet D.、Bailey James L.、Kovalik Jean‐Paul、Rauh Manfred、Karbach Susanne、Hilgers Karl F.、Luft Friedrich、Nishiyama Akira、Nakano Daisuke、Kitada Kento、Titze Jens
    • Journal Title

      Acta Physiologica

      Volume: 00 Issue: 1

    • DOI

      10.1111/apha.13629

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 高血圧学におけるモデル動物の再考: ワンポイント測定の落とし穴2021

    • Author(s)
      北田研人
    • Organizer
      第43回日本高血圧学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Water conservation system -多臓器に制御される水・ナトリウム代謝-2021

    • Author(s)
      北田研人
    • Organizer
      第64回日本腎臓学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 腎機能低下に伴う体液変化とサルコペニア2020

    • Author(s)
      北田研人
    • Organizer
      第11回日本腎臓リハビリテーション学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-09-29   Modified: 2023-01-30  

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