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

Elucidation of the pathogenesis and development of new diagnostic and therapeutic strategy of kidney disease based on mechanobiology

Research Project

Project/Area Number 20K08616
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionKyorin University

Principal Investigator

NAGASE Miki  杏林大学, 医学部, 教授 (60302733)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsメカノバイオロジー / Piezo2 / メサンギウム細胞 / 傍糸球体レニン産生細胞 / 血管外膜線維芽細胞 / 急性腎障害 / 慢性腎臓病 / 高血圧性腎障害 / 線維芽細胞 / 非ステロイド型選択的MRブロッカー / 傍糸球体細胞 / レニン / メカノセンサー
Outline of Research at the Start

腎臓の細胞は、血流や尿流に起因するメカノ刺激にさらされているが、その感知応答機構は不明な点が多い。本研究では、メカノセンサー分子、特にTRPV2とPiezo2に着目し、急性腎障害や慢性腎臓病の病態解明と新規診断法・治療薬開発を目指す。
本目的を達成するために、①TRPV2の尿細管障害における役割、②Piezo2の糸球体・腎病変における役割、③腎求心性感覚神経に発現するメカノセンサーの同定と難治性高血圧における役割、④腎障害の三次元イメージング、の4目標を設定し、当該分子の局在や上流・下流因子を決定し、疾患モデル動物や阻害薬、遺伝子改変マウスを用いた解析を実施する。

Outline of Final Research Achievements

Kidney cells are exposed to various mechanical stimuli caused by blood flow, blood pressure, and urinary flow, but their sensing and response mechanisms remain largely elusive. In this study, we focused on the mechanosensor molecule Piezo2, and found that in the normal kidney, Piezo2 expression was restricted to the glomerular mesangial cells and juxtaglomerular renin-producing cells. In the developing metanephros, Piezo2 was expressed in the Foxd1-positive mesenchymal progenitor cells and their lineage cells. In dehydration mice, its expression was decreased in the mesangial cells, while increased in the renin cells. In hypertensive nephrosclerosis models with glomerular hypertension, Piezo2 expression was enhanced in the mesangial cells, some renin-producing cells, and perivascular collagen-producing cells, which was normalized by antihypertensive treatment with mineralocorticoid receptor antagonist. These results suggest the role of Piezo2 in the pathogenesis of kidney diseases.

Academic Significance and Societal Importance of the Research Achievements

糖尿病・高血圧などを発症基盤とする慢性腎臓病(CKD)や、救急医療や集中治療室患者で頻度の高い急性腎障害(AKI)は、患者の生命予後やQOLに大きく影響する疾患であるが、未だ有効な治療法がない。現在Piezo2阻害の影響を解析しているが、メカノ感受応答システムの入り口にあたるメカノセンサーPiezo2は、腎臓病治療法の新たな標的として有望と考えられる。CKDやAKIに対し、病態に基づく特効薬が開発されれば、透析を必要としない健康な長寿社会が期待される。

Report

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

    (15 results)

All 2023 2022 2021 2020 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (2 results)

  • [Journal Article] Upregulation of Piezo2 in the mesangial, renin, and perivascular mesenchymal cells of the kidney of Dahl salt-sensitive hypertensive rats and its reversal by esaxerenone2023

    • Author(s)
      Ochiai Koji、Mochida Yuki、Nagase Takashi、Fukuhara Hiroshi、Yamaguchi Yoshihiro、Nagase Miki
    • Journal Title

      Hypertension Research

      Volume: - Issue: 5 Pages: 1234-1246

    • DOI

      10.1038/s41440-023-01219-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excised human larynx in N-vinyl-2-pyrrolidone-embalmed cadavers can produce voiced sound by pliable vocal fold vibration.2022

    • Author(s)
      Miyamoto M, Nagase M, Watanabe I, Nakagawa H, Karita K, Tsuji DH, Montagnoli AN, Matsumura G, Saito K.
    • Journal Title

      Anat Sci Int

      Volume: in press Issue: 4 Pages: 347-357

    • DOI

      10.1007/s12565-021-00646-3

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Formalin-free soft embalming of human cadavers using N-vinyl-2-pyrrolidone: perspectives for cadaver surgical training and medical device development.2022

    • Author(s)
      Nagase M, Nagase T, Tokumine J, Saito K, Sunami E, Shiokawa Y, Matsumura G.
    • Journal Title

      Anat Sci Int

      Volume: in press Issue: 3 Pages: 273-282

    • DOI

      10.1007/s12565-022-00664-9

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Piezo2 expression and its alteration by mechanical forces in mouse mesangial cells and renin-producing cells2022

    • Author(s)
      Mochida Yuki、Ochiai Koji、Nagase Takashi、Nonomura Keiko、Akimoto Yoshihiro、Fukuhara Hiroshi、Sakai Tatsuo、Matsumura George、Yamaguchi Yoshihiro、Nagase Miki
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4197-4197

    • DOI

      10.1038/s41598-022-07987-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photoacoustic needle improves needle tip visibility during deep peripheral nerve block.2021

    • Author(s)
      Watanabe K, Tokumine J, Lefor AK, Nakazawa H, Yamamoto K, Karasawa H, Nagase M, Yorozu T.
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1 Pages: 8432-8432

    • DOI

      10.1038/s41598-021-87777-9

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Physiological and pathological roles of Piezo2 in the kidney2023

    • Author(s)
      Miki Nagase
    • Organizer
      International Symposium on Mechanobiology for Human Health:8 years progress in The AMED-CREST/PRIME project on mechanobiology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Piezo2は糸球体メサンギウム細胞とレニン産生細胞に発現し、糸球体内圧低下に伴い細胞特異的に増減する2022

    • Author(s)
      持田勇希、落合剛二、長瀬美樹
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Piezo2 expression and its alteration by mechanical forces in mouse mesangial cells and renin-producing cells2022

    • Author(s)
      Yuki Mochida、Koji Ochiai、Miki Nagase
    • Organizer
      International Society of Hypertension
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] メカノセンサーPiezo2の体液恒常性維持への関与2022

    • Author(s)
      持田勇希、長瀬美樹、山口芳裕
    • Organizer
      第50回日本救急医学会総会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 鉱質コルチコイド受容体活性化と食塩感受性高血圧、慢性腎臓病2021

    • Author(s)
      長瀬美樹
    • Organizer
      第50回日本心脈管作動物質学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] MR関連高血圧の新たな展開2021

    • Author(s)
      長瀬美樹
    • Organizer
      第51回日本腎臓学会 東部学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Mechanical forcees acting on renal cells and their sensing mechaniams.2021

    • Author(s)
      Nagase M
    • Organizer
      The Joint Meeting of the 126th Annual Meeting of the Japanese Association of Anatomists the 98th Annial Meeting of the Physilogical Society
    • Related Report
      2020 Research-status Report
  • [Presentation] 鉱質コンチコイド受容体活性化と慢性腎臓病2020

    • Author(s)
      長瀬美樹
    • Organizer
      第56回日本高血圧関連疾患モデル学会学術総会
    • Related Report
      2020 Research-status Report
  • [Remarks] 杏林大学医学部肉眼解剖学教室

    • URL

      https://www.kyorin-u.ac.jp/univ/graduate/medicine/education/departments/macro-anat/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 腎臓におけるメカノチャネルPiezo2の発現とその役割の解明

    • URL

      http://www.kyorin-u.ac.jp/univ/faculty/medicine/news/2022/03/news220330piezo2.php

    • Related Report
      2021 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi