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

Molecular mechanism of Na+/Ca2+ exchanger regulation in renal distal tubules

Research Project

Project/Area Number 20K07302
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48030:Pharmacology-related
Research InstitutionFukuoka University

Principal Investigator

Iwamoto Takahiro  福岡大学, 医学部, 教授 (20300973)

Co-Investigator(Kenkyū-buntansha) 喜多 知  福岡大学, 医学部, 講師 (50797107)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsイオン輸送体 / 遠位尿細管 / Ca2+再吸収 / Ca2+シグナル / 遺伝子改変マウス / カルシウム / 副甲状腺ホルモン
Outline of Research at the Start

副甲状腺ホルモンは、腎臓のCa2+再吸収を亢進することが知られているが、その詳細な分子機序は未だ不明である。Na+/Ca2+交換輸送体は遠位尿細管の基底側膜に主に発現し、Ca2+再吸収に関与すると考えられている。本研究では、副甲状腺ホルモンがNa+/Ca2+交換輸送体の細胞膜発現制御を介して、腎臓のCa2+再吸収を亢進する機序について、in vitro & in vivo実験系により実証する。本研究の成果は、Ca2+代謝異常症の病態解明や新規治療法の開発に繋がることが期待される。

Outline of Final Research Achievements

Na+/Ca2+ exchanger type 1 (NCX1) is abundantly expressed on the basolateral membrane of the distal tubule and is thought to be involved in renal Ca2+ reabsorption. However, the localization mechanism of NCX1 to the basolateral membrane and the regulation mechanism of transport by hormones and physiologically active substances have not been fully elucidated. In this study, we generated MDCK cells transfected with an NCX1 mutant with abnormal membrane localization and its knock-in and transgenic mice, and experimentally found that the localization of NCX1 to the basolateral membrane is regulated by various receptor stimuli, leading to the modulation of Ca2+ reabsorption.

Academic Significance and Societal Importance of the Research Achievements

1型Na+/Ca2+交換輸送体(NCX1)は、細胞膜を介して3個のNa+と1個のCa2+を交換輸送する重要なCa2+トランスポーター(輸送担体)であり、Ca2+ホメオスタシス(恒常性)の維持やCa2+シグナルの形成に関わっている。本研究では、遠位尿細管基底側膜へのNCX1発現局在が各種受容体刺激により調節され、腎臓のCa2+再吸収が制御されることをin vitro & in vivo実験系により実証した。本研究の成果により、Ca2+代謝異常症(高Ca血症、低Ca血症)に関する病因・病態の解明が進むとともに、新規治療法の開発に繋がることが期待される。

Report

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

    (21 results)

All 2023 2022 2021 2020 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 2 results) Remarks (3 results)

  • [Journal Article] Functional characteristics and therapeutic potential of SLC41 transporters.2023

    • Author(s)
      Nemoto T, Tagashira H, Kita T, Kita S, Iwamoto T.
    • Journal Title

      J Pharmacol Sci.

      Volume: 151(2) Issue: 2 Pages: 88-92

    • DOI

      10.1016/j.jphs.2022.12.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Sigma-1 receptor: Pathophysiological roles and therapeutic potential in neurodegenerative diseases.2023

    • Author(s)
      Shinoda Y, Nemoto T, Iwamoto T.
    • Journal Title

      Med Bull Fukuoka Univ

      Volume: 50 Pages: 43-48

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of transient receptor potential cation channel?6 promotes capillary arterialization during post‐ischaemic blood flow recovery2022

    • Author(s)
      Numaga‐Tomita Takuro、Shimauchi Tsukasa、Kato Yuri、Nishiyama Kazuhiro、Nishimura Akiyuki、Sakata Kosuke、Inada Hiroyuki、Kita Satomi、Iwamoto Takahiro、Nabekura Junichi、Birnbaumer Lutz、Mori Yasuo、Nishida Motohiro
    • Journal Title

      British Journal of Pharmacology

      Volume: 180 Issue: 1 Pages: 94-110

    • DOI

      10.1111/bph.15942

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Na+/Ca2+ exchanger mediates cold Ca2+ signaling conserved for temperature-compensated circadian rhythms2021

    • Author(s)
      Kon Naohiro、Wang Hsin-tzu、Kato Yoshiaki S.、Uemoto Kyouhei、Kawamoto Naohiro、Kawasaki Koji、Enoki Ryosuke、Kurosawa Gen、Nakane Tatsuto、Sugiyama Yasunori、Tagashira Hideaki、Endo Motomu、Iwasaki Hideo、Iwamoto Takahiro、Kume Kazuhiko、Fukada Yoshitaka
    • Journal Title

      Science Advances

      Volume: 7 Issue: 18 Pages: 1-12

    • DOI

      10.1126/sciadv.abe8132

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic knockout and pharmacologic inhibition of NCX1 attenuate hypoxia-induced pulmonary arterial hypertension.2020

    • Author(s)
      1.Nagata A, Tagashira H, Kita S, Kita T, Nakajima N, Abe K, Iwasaki A, Iwamoto T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 529(3) Issue: 3 Pages: 793-798

    • DOI

      10.1016/j.bbrc.2020.06.045

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SLC41 Mg2+輸送体の最近の話題2020

    • Author(s)
      岩本隆宏
    • Journal Title

      マグネシウム

      Volume: 39 Pages: 30-36

    • Related Report
      2020 Research-status Report
  • [Presentation] NCX輸送体を標的とした肺高血圧症治療戦略2023

    • Author(s)
      岩本隆宏
    • Organizer
      第52回日本心脈管作動物質学会シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 虚血性急性腎不全発症における遠位尿細管Caオーバーロードの重要性2022

    • Author(s)
      根本隆行、若崎るみ枝、喜多知、中嶋尚子、喜多紗斗美、岩本隆宏
    • Organizer
      第6回 日本臨床薬理学会 九州・沖縄地方会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 遠位尿細管特異的NCX1欠損/高発現マウスを用いた急性腎障害機序の解析2022

    • Author(s)
      根本隆行、若崎るみ枝、田頭秀章、喜多知、中嶋尚子、喜多紗斗美、岩本隆宏
    • Organizer
      第51回日本心脈管作動物質学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 阻害薬非感受性NCX1変異体ノックインマウスを用いた薬効評価系の確立2022

    • Author(s)
      喜多知、篠田康晴、根本隆行、小松知広、上原吉就、喜多紗斗美、岩本隆宏
    • Organizer
      第75回 日本薬理学会西南部会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 虚血性急性腎障害における遠位尿細管NCX1の重要性 第41回 日本マグネシウム学会学術集会2022

    • Author(s)
      根本隆行、若崎るみ枝、喜多知、中嶋尚子、喜多紗斗美、岩本隆宏
    • Organizer
      第41回 日本マグネシウム学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Mild hypomagnesemia and increased vulnerability to catecholamine-induced arrhythmias in CNNM2-deficient mice.2021

    • Author(s)
      Tagashira H, Nemoto T, Kita T, Tsujita Y, Kita S, Iwamoto T.
    • Organizer
      The 40th Annual Meeting of Japanese Society for Magnesium Research
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] NCX1を標的とした肺高血圧症の治療戦略2021

    • Author(s)
      喜多紗斗美、田頭秀章、岩本隆宏
    • Organizer
      第95回日本薬理学会年会シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 体内時計におけるNa+/Ca2+交換輸送体の役割とその創薬応用2021

    • Author(s)
      金尚宏、岩本隆宏、深田吉孝
    • Organizer
      第95回日本薬理学会年会シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] TRPM7/CNNM2遺伝子改変マウスを用いたMg代謝異常による心血管病態解析2021

    • Author(s)
      田頭秀章、喜多紗斗美、岩本隆宏
    • Organizer
      日本薬学会第142年会シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 心筋特異的NCX1ノックアウトマウスの突然死の特性2021

    • Author(s)
      田頭秀章、喜多紗斗美、岩本隆宏
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 褐色脂肪組織熱産生におけるNCX1の機能的役割2021

    • Author(s)
      喜多知、田頭秀章、根本隆行、喜多紗斗美、岩本隆宏
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] The pathophysiological role of vascular smooth muscle NCX1 for pulmonary arterial hypertension.2020

    • Author(s)
      Tagashira H, Nagata A, Kita T, Kita S, Iwamoto T.
    • Organizer
      65th Biophysical Society Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Remarks] 福岡大学医学部薬理学

    • URL

      https://www.med.fukuoka-u.ac.jp/pharmaco/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 福岡大学医学部薬理学

    • URL

      https://www.med.fukuoka-u.ac.jp/pharmaco/index.html

    • Related Report
      2021 Research-status Report
  • [Remarks] 福岡大学医学部薬理学

    • URL

      http://www.med.fukuoka-u.ac.jp/pharmaco/index.html

    • Related Report
      2020 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