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The role of mechanosensitive TRPC6 channel in cell cycle progression of bone marrow mesenchymal stem cells

Research Project

Project/Area Number 18K12047
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionSano Nihon University College (2021-2023)
Fukuoka University (2018-2020)

Principal Investigator

Ichikawa Jun  佐野日本大学短期大学, その他部局等, 准教授(移行) (70368207)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords骨髄間葉系幹細胞 / イオンチャネル / TRPC6 / 機械刺激 / 細胞周期 / 増殖 / 細胞骨格 / 再生医療 / TRPC6チャネル
Outline of Final Research Achievements

Bone marrow mesenchymal stem cells (BMSCs) can be used as a reliable therapeutic resource for regenerative medicine and bioengineering. Controlling the proliferative potential and cell cycle progression of BMSCs is an attractive approach to maximising the yield of BMSCs during expansion in vitro. In this study, we explored the contribution of TRPC6 channel, which is a mechanosensitive Ca2+-permeable cation channel, in cell cycle progression of BMSCs. The mechanical potentiation of receptor-activated TRPC6 channel was enhanced at M phase. The proliferative activity was enhanced by the synergistic activation of TRPC6 channel by receptor and mechanical stimulation. We also investigated the intracellular molecules relating to the TRPC6-mediated mechanosensitive signaling pathways.

Academic Significance and Societal Importance of the Research Achievements

圧刺激やずり応力等の機械的刺激は生体の組織や細胞のシグナル伝達経路にはたらきかけ、増殖をはじめ様々な応答を引き起こす。再生医療分野で臨床的に広く用いられている骨髄間葉系幹細胞もまた機械刺激に対し感受性を示し、機械刺激が分化の方向決定等重要な制御に関与することがわかっているが、メカニズムに関しては不明な点も多い。本研究ではTRPC6が機械刺激を細胞周期制御シグナルに変換する重要な分子であることを明らかにした。さらにこの結果を応用すれば増殖効率が向上することを示した。この方法で得られた細胞は癌化のおそれがなく分化能も正常に維持されていたため、安全で効率的な新しい培養方法の確立に繋がると期待される。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (24 results)

All 2024 2023 2022 2021 2019 2018 Other

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Remarks (6 results)

  • [Journal Article] Contribution of Coiled-Coil Assembly to Ca2+/Calmodulin-Dependent Inactivation of TRPC6 Channel and its Impacts on FSGS-Associated Phenotypes2019

    • Author(s)
      Polat Onur K.、Uno Masatoshi、Maruyama Terukazu、Tran Ha Nam、Imamura Kayo、Wong Chee Fah、Sakaguchi Reiko、Ariyoshi Mariko、Itsuki Kyohei、Ichikawa Jun、Morii Takashi、Shirakawa Masahiro、Inoue Ryuji、Asanuma Katsuhiko、Reiser Jochen、Tochio Hidehito、Mori Yasuo、Mori Masayuki X.
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: 30 Issue: 9 Pages: 1587-1603

    • DOI

      10.1681/asn.2018070756

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TRPCサブファミリーの分子構造と活性化・制御機序の新知見2019

    • Author(s)
      井上隆司, 市川純, 崔媛媛
    • Journal Title

      医学のあゆみ

      Volume: 270 Pages: 876-882

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] TRPM7-mediated spontaneous Ca2+ entry regulates the proliferation and differentiation of human leukemia cell line K5622018

    • Author(s)
      Takahashi Kiriko、Umebayashi Chisato、Numata Tomohiro、Honda Akira、Ichikawa Jun、Hu Yaopeng、Yamaura Ken、Inoue Ryuji
    • Journal Title

      Physiological Reports

      Volume: 6 Issue: 14 Pages: e13796-e13796

    • DOI

      10.14814/phy2.13796

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腎糸球体ポドサイトTRPC6チャネルの機械刺激感受性および濾過障壁機能に対するcGMPの効果.2024

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第101回日本生理学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 腎糸球体ポドサイトTRPC6チャネルの受容体・機械刺激の協働作用による濾過障壁機能の強化とcGMPの効果.2023

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第149回日本薬理学会関東部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 受容体・機械共刺激による腎糸球体ポドサイトの濾過障壁機能強化に対するcGMPの効果.2023

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 機械刺激応答チャネルTRPC6による腎糸球体濾過機構制御と機能破綻の関連.2022

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第15回栃木県栄養改善学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] FSGSの原因となる腎糸球体ポドサイトTRPC6チャネルN端変異は受容体・機械刺激応答およびタンパク濾過障壁機能に影響を及ぼす.2022

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 受容体・機械刺激によるTRPC6活性化が腎糸球体ポドサイトの濾過障壁機能に及ぼす影響.2022

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 受容体・機械刺激によるTRPC6の同時刺激が腎糸球体ポドサイトの濾過障壁機能を増強する.2022

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第99回日本生理学会年大会
    • Related Report
      2021 Research-status Report
  • [Presentation] TRPC6チャネルのFSGS変異が腎糸球体ポドサイトのタンパク濾過障害に及ぼす影響.2021

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第251回生理学東京談話会
    • Related Report
      2021 Research-status Report
  • [Presentation] TRPC6チャネルのFSGS変異が腎糸球体ポドサイトのタンパク濾過機能に及ぼす影響.2021

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第20回氷川フォーラム
    • Related Report
      2021 Research-status Report
  • [Presentation] 骨髄間質細胞における細胞周期進行へのTRPC6機械刺激感受性の関与2019

    • Author(s)
      市川純、井上隆司
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of electrically-modulated molecules that enhance bone marrow stromal cell proliferation.2019

    • Author(s)
      Jun Ichikawa, Ryuji Inoue
    • Organizer
      9th FAOPS (Federation of the Asian and Oceanian Physiological Societies) Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A multi-hierarchical study on the arrhythmogenicity of a Ca-activated cation channel TRPM4.2019

    • Author(s)
      Ryuji Inoue, Yaopeng Hu, Yanghua Shen, Keizo Hiraishi, Lin Hai-Kurahara, Jun Ichikawa, Tomohiro Numata, Xin Zhu
    • Organizer
      9th FAOPS (Federation of the Asian and Oceanian Physiological Societies) Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腎スリット膜メカノセンサーpodocinは受容体刺激で活性化されたTRPC6チャネルの機械刺激応答の増強を制御する.2019

    • Author(s)
      市川 純、中川 緑、井上隆司
    • Organizer
      第92回日本薬理学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] An integrative approach to investigating remodeling-associated arrhythmias: Computer simulation based on the gating analysis of TRPM4 channel.2018

    • Author(s)
      Ryuji Inoue, Yaopeng Hu, Lin-Hai Kurahara, Jun Ichikawa, Tomohiro Numata, Yanghua Sheng, Wenfeng Sheng, Xin Zhu.
    • Organizer
      16th Nanjing Course on Cardiac Revascularization & ACS Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A theoretical approach to investigating the arrhythmogenicity of TRPM4 channel.2018

    • Author(s)
      Ryuji Inoue, Yaopeng Hu, Lin-Hai Kurahara, Jun Ichikawa, Tomohiro Numata, Yanghua Sheng, Xin Zhu.
    • Organizer
      NCCR TransCure Lecture
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] researchmap(市川 純)

    • URL

      https://researchmap.jp/read0144341/

    • Related Report
      2023 Annual Research Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/read0144341/

    • Related Report
      2021 Research-status Report
  • [Remarks] ResearchMap

    • URL

      https://researchmap.jp/read0144341/

    • Related Report
      2020 Research-status Report
  • [Remarks] 福岡大学研究者情報(「市川純」で検索)

    • URL

      https://resweb2.jhk.adm.fukuoka-u.ac.jp/FukuokaUniv/R101J_Action.do

    • Related Report
      2019 Research-status Report
  • [Remarks] 福岡大学医学部生理学・大学院医学研究科細胞分子制御学ホームページ

    • URL

      http://www.med.fukuoka-u.ac.jp/physiol/study4.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 福岡大学医学部生理学・大学院医学研究科細胞分子制御学HP

    • URL

      http://www.med.fukuoka-u.ac.jp/physiol/study.html

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2025-01-30  

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