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Mechanism of direct renal control by the autonomic nervous system

Research Project

Project/Area Number 20K17242
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53040:Nephrology-related
Research InstitutionNagasaki University

Principal Investigator

Inoue Tsuyoshi  長崎大学, 医歯薬学総合研究科(医学系), 教授 (30821665)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腎臓 / 自律神経
Outline of Research at the Start

多くの方が腎臓病に患う一方,腎臓病の根本的な治療法はいまだに存在せず,新たな治療法の開発は喫緊の課題である.予備実験において,尿細管細胞に障害を与える際に,神経伝達物質受容体アゴニストを投与すると,細胞が保護されるという結果が得られた.腎臓は神経支配(特に交感神経)が非常に豊富な臓器であることを考慮すると,神経を介した腎臓の細胞への直接的な影響も考えられた.そこで,本申請では,自律神経が直接的に腎臓細胞に与える影響に着目し,神経伝達物質に対する受容体を持つ腎臓細胞の生体内での役割・活性化メカニズムについての解析を進める.これらの成果を基盤に,革新的な創薬の標的分子の探索を目指す.

Outline of Final Research Achievements

We found that vagus nerve stimulation alleviated renal injury after cisplatin-induced kidney injury, and that nerve stimulation suppressed macrophage influx into the kidney. Using knockout mice, we found that the α7 acetylcholine receptor on macrophages plays an important role in exerting anti-inflammatory and renal protective effects. We also found that sympathetic nerve stimulation also protects the kidneys. We found that sympathetic nerve stimulation induces Tim3 expression via β2 adrenergic receptors on macrophages, leading to proximal tubular protection. Furthermore, we found that tubular cells are directly protected by β2-adrenoceptor stimulation.

Academic Significance and Societal Importance of the Research Achievements

多くの方が腎臓病を患う一方、腎臓病の根本的な治療法はいまだに存在せず、新たな治療法の開発は喫緊の課題である。本研究によって、障害後においても迷走神経刺激が腎臓保護・治療効果を発揮するメカニズムや、交感神経刺激によるマクロファージを介した腎保護メカニズムなど、神経系を介した新規の腎臓保護作用メカニズムの一端を解明することができた。今後さらに研究を進めることで、腎臓病の新規の治療法開発につなげていきたい。

Report

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

    (19 results)

All 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 10 results)

  • [Int'l Joint Research] バージニア大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] バージニア大学(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Activation of α7 nicotinic acetylcholine receptors attenuates monocyte endothelial adhesion through FUT7 inhibition2022

    • Author(s)
      Wu Chia-Hsien、Inoue Tsuyoshi、Nakamura Yasuna、Uni Rie、Hasegawa Sho、Maekawa Hiroshi、Sugahara Mai、Wada Youichiro、Tanaka Tetsuhiro、Nangaku Masaomi、Inagi Reiko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 590 Pages: 89-96

    • DOI

      10.1016/j.bbrc.2021.12.094

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysophosphatidylcholine mediates fast decline in kidney function in diabetic kidney disease2022

    • Author(s)
      Yoshioka Kentaro、Hirakawa Yosuke、Kurano Makoto、Ube Yuko、Ono Yoko、Kojima Kensuke、Iwama Taiga、Kano Kuniyuki、Hasegawa Sho、Inoue Tsuyoshi、Shimada Takashi、Aoki Junken、Yatomi Yutaka、Nangaku Masaomi、Inagi Reiko
    • Journal Title

      Kidney International

      Volume: 101 Issue: 3 Pages: 510-526

    • DOI

      10.1016/j.kint.2021.10.039

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury2021

    • Author(s)
      Tanaka Shinji、Abe Chikara、Abbott Stephen B. G.、Zheng Shuqiu、Yamaoka Yusuke、Lipsey Jonathan E.、Skrypnyk Nataliya I.、Yao Junlan、Inoue Tsuyoshi、Nash William T.、Stornetta Daniel S.、Rosin Diane L.、Stornetta Ruth L.、Guyenet Patrice G.、Okusa Mark D.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 12

    • DOI

      10.1073/pnas.2021758118

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Decreased IFT88 expression with primary cilia shortening causes mitochondrial dysfunction in cisplatin-induced tubular injury2021

    • Author(s)
      Fujii Rie、Hasegawa Sho、Maekawa Hiroshi、Inoue Tsuyoshi、Yoshioka Kentaro、Uni Rie、Ikeda Yoichiro、Nangaku Masaomi、Inagi Reiko
    • Journal Title

      American Journal of Physiology-Renal Physiology

      Volume: 321 Issue: 3 Pages: F278-F292

    • DOI

      10.1152/ajprenal.00673.2020

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroimmune system-mediated renal protection mechanisms2021

    • Author(s)
      Inoue Tsuyoshi
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 25 Issue: 9 Pages: 915-924

    • DOI

      10.1007/s10157-021-02062-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells2020

    • Author(s)
      Higashijima Y, Matsui Y, Shimamura T, Nakaki R, Nagai N, Tsutsumi S, Abe Y, Link VM, Osaka M, Yoshida M, Watanabe R, Tanaka T, Taguchi A, Miura M, Ruan X, Li G, Inoue T, Nangaku M, Kimura H, Furukawa T, Aburatani H, Wada Y, Ruan Y, Glass CK, Kanki Y
    • Journal Title

      The EMBO Journal

      Volume: 39 Issue: 7 Pages: 1-1

    • DOI

      10.15252/embj.2019103949

    • NAID

      120006902140

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vagus nerve stimulation even after injury ameliorates cisplatin-induced nephropathy via reducing macrophage infiltration2020

    • Author(s)
      Uni Rie、Inoue Tsuyoshi、Nakamura Yasuna、Fukaya Daichi、Hasegawa Sho、Wu Chia-Hsien、Fujii Rie、Surattichaiyakul Bongkod、Peerapanyasut Wachirasek、Ozeki Atsuko、Akimitsu Nobuyoshi、Wada Youichiro、Nangaku Masaomi、Inagi Reiko
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 9472-9472

    • DOI

      10.1038/s41598-020-66295-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 自律神経-免疫系を介した抗炎症・臓器保護メカニズム2022

    • Author(s)
      井上 剛
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 自律神経制御による腎不全予防戦略2022

    • Author(s)
      井上 剛
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Elucidation of anti-inflammatory and kidney protection mechanisms through nervous-immune systems using single cell RNA-seq2022

    • Author(s)
      井上 剛
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 自律神経-免疫系を介した抗炎症メカニズム(Anti-inflammatory mechanism through autonomic-immune system)2021

    • Author(s)
      井上 剛
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会 合同大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Role of macrophages in the protective effect of the kidney through the autonomic nervous system2021

    • Author(s)
      井上 剛
    • Organizer
      ERA-EDTA-JSN joint symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脳腎連関を介した腎疾患進展抑制メカニズム2021

    • Author(s)
      井上 剛
    • Organizer
      第51回日本腎臓学会西部学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] バージニア大学腎臓内科留学2021

    • Author(s)
      井上 剛
    • Organizer
      第44回日本分子生物学学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 自律神経-免疫系を介した抗炎症メカニズム(Anti-inflammatory mechanism through autonomic-immune system)2021

    • Author(s)
      井上 剛
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会 合同大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Neuro-immune systems-mediated renal protection mechanism2020

    • Author(s)
      井上 剛
    • Organizer
      第63回日本腎臓学会学術大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 自律神経系による炎症制御におけるマクロファージの役割2020

    • Author(s)
      井上 剛
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2023-01-30  

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