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Physiological and pathophysiological significance of NBCn2 in luminal acid secretion in proximal tubules.

Research Project

Project/Area Number 18K08201
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionThe University of Tokyo (2020-2021)
Tokyo Gakugei University (2018-2019)

Principal Investigator

SUZUKI MASASHI  東京大学, 医学部附属病院, 届出研究員 (90595662)

Co-Investigator(Kenkyū-buntansha) 堀田 晶子  東京大学, 医学部附属病院, 届出診療員 (20534895)
中村 元信  東京大学, 医学部附属病院, 助教 (40459524)
佐藤 信彦  東京大学, 医学部附属病院, 助教 (80572552)
山崎 修  帝京大学, 医学部, 講師 (80757229)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsNBCn2 / 近位尿細管 / 酸塩基平衡 / 腎臓内科学
Outline of Final Research Achievements

Sodium-dependent acid-base transport in the lumenal side of the proximal tubule has been questioned, although NHE3 is thought to be mainly responsible for sodium-dependent acid-base transport. In the present study, we analyzed acid-base transport in isolated proximal tubules and found that the NHE inhibitor EIPA suppressed acid-base transport by 10-50%, whereas DIDS suppressed it by 30-50% and simultaneous addition of EIPA and DIDS by more than 80%. siRNA against NBCn2 suppressed acid-base transport in the proximal tubular lumen by about 50%, and immunohistochemistry confirmed the expression of NBCn2. NBCn2 expression on the proximal tubular lumen may be involved in acid-base transport.

Academic Significance and Societal Importance of the Research Achievements

本研究では主にNa/H交換輸送体(NHE)3が司るとされてきた近位尿細管管腔側のナトリウム依存性酸塩基輸送がNHE3だけでなくNa-HCO3共輸送体NBCn2により行われていることを示すことができた。ナトリウムは血液中の主要な電解質であり、血圧のコントロールに重要な役割を果たしている。一方、近位尿細管は糸球体で濾過されたナトリウムの約80%を再吸収しており、今後血圧調節のメカニズム解明や新たな降圧剤開発に貢献できる可能性がある。

Report

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

    (13 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Insulin promotes sodium transport but suppresses gluconeogenesis via distinct cellular pathways in?human and rat renal proximal tubules2020

    • Author(s)
      Nakamura Motonobu、Tsukada Hiroyuki、Seki George、Satoh Nobuhiko、Mizuno Tomohito、Fujii Wataru、Horita Shoko、Moriya Kyoji、Sato Yusuke、Kume Haruki、Nangaku Masaomi、Suzuki Masashi
    • Journal Title

      Kidney International

      Volume: 97 Issue: 2 Pages: 316-326

    • DOI

      10.1016/j.kint.2019.08.021

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrolyte transport in the renal collecting duct and its regulation by the renin–angiotensin–aldosterone system2019

    • Author(s)
      Yamazaki Osamu、Ishizawa Kenichi、Hirohama Daigoro、Fujita Toshiro、Shibata Shigeru
    • Journal Title

      Clinical Science

      Volume: 133 Issue: 1 Pages: 75

    • DOI

      10.1042/cs20180194

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Calcineurin dephosphorylates Kelch-like 3, reversing phosphorylation by angiotensin II and regulating renal electrolyte handling2019

    • Author(s)
      Ishizawa Kenichi、Wang Qin、Li Jinping、Yamazaki Osamu、Tamura Yoshifuru、Fujigaki Yoshihide、Uchida Shunya、Lifton Richard P.、Shibata Shigeru
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 8 Pages: 3155

    • DOI

      10.1073/pnas.1817281116

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of cl<sup>−</sup> signaling and ion transport by recruitment of kinases and phosphatases mediated by the regulatory protein IRBIT2018

    • Author(s)
      Vachel Laura、Shcheynikov Nikolay、Yamazaki Osamu、Fremder Moran、Ohana Ehud、Son Aran、Shin Dong Min、Yamazaki-Nakazawa Ai、Yang Chin-Rang、Knepper Mark A.、Muallem Shmuel
    • Journal Title

      Science Signaling

      Volume: 11 Issue: 554

    • DOI

      10.1126/scisignal.aat5018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 副甲状腺ホルモンはPKC/FOXO1を介して近位尿細管糖新生を亢進させる2019

    • Author(s)
      塚田 弘之、中村 元信、水野 智仁、佐藤 信彦、佐藤 悠佑、堀田 晶子、関 常司、久米 春喜、南学 正臣、鈴木 正志
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Parathyroid Hormone Enhances Gluconeogenesis via the PKC/FoxO1 Pathway in Proximal Tubules2019

    • Author(s)
      Hiroyuki Tsukada, Motonobu Nakamura, Shoko Horita, Wataru Fujii, Tomohito Mizuno, Nobuhiko Satoh, Yusuke Sato, George Seki, Haruki Kume, Masaomi Nangaku, Masashi Suzuki.
    • Organizer
      Annual Meeting of The American Society of Nephrology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Insulin Stimulates V-ATPase on Renal Proximal Tubules via the Akt/mTORC2 Pathway2019

    • Author(s)
      Motonobu Nakamura, Nobuhiko Satoh, Hiroyuki Tsukada, Tomohito Mizuno, Wataru Fujii, Shoko Horita, Masaomi Nangaku, Masashi Suzuki
    • Organizer
      Annual Meeting of The American Society of Nephrology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ROLES OF NA+/HCO3- COTRANSPORTER NBCN2 IN ACID-BASE TRANSPORT IN THE APICAL MEMBRANE OF RENAL PROXIMAL TUBULES2019

    • Author(s)
      Nakamura, M, Suzuki, A, Horita, S, Satoh, N, Tsukada, H, Sato, Y, Seki, G, Kume, H, Nangaku, M, Suzuki, M
    • Organizer
      ISN World Congress of Nephrology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] EFFECTS OF PARATHYROID HORMONE ON GLUCOSE METABOLISM IN RENAL PROXIMAL TUBULES2019

    • Author(s)
      Tsukada, H, Nakamura, M, Satoh, N, Mizuno, T, Sato, Y, Horita, S, Seki, G, Kume, H, Nangaku, M, Suzuki, M
    • Organizer
      ISN World Congress of Nephrology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 近位尿細管ナトリウム輸送調節におけるWNK1/OSR1経路の意義2018

    • Author(s)
      中村元信、佐藤信彦、塚田弘之、水野智仁、佐藤悠佑、堀田晶子、関常司、鈴木正志、久米春喜、南学正臣
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 副甲状腺ホルモンは近位尿細管ナトリウム輸送と糖新生に関与している2018

    • Author(s)
      塚田 弘之、佐藤信彦、中村 元信、水野智仁、佐藤悠佑、堀田晶子、関常司、鈴木正志、久米春喜、南学正臣
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] A Pivotal Role of WNK1/OSR1 Pathway in Regulation of Renal Proximal2018

    • Author(s)
      Motonobu Nakamura, Shoko Horita, Nobuhiko Satoh, George Seki, Tomohito Mizuno, Hiroyuki Tsukada, Yusuke Sato, Haruki Kume, Masaomi Nangaku, Masashi Suzuki.
    • Organizer
      Annual Meeting of The American Society of Nephrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A Novel I551F Mutant of Na+/HCO3- Cotransporter NBCe1 Has Cytosolic Retention and Diminishes Transport Activity2018

    • Author(s)
      Osamu Yamazaki, Maho Yamashita, Jinping Li, Tadashi Yoshida, Junichi Hirahashi, Shigeru Shibata, Matsuhiko Hayashi.
    • Organizer
      Annual Meeting of The American Society of Nephrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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