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Mechanism and physiological role of urinary excretion of aquaporin-2

Research Project

Project/Area Number 15K09301
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionMeiji Pharmaceutical University

Principal Investigator

SASAKI SEI  明治薬科大学, 薬学部, 客員研究員 (60170677)

Co-Investigator(Kenkyū-buntansha) 田中 靖子  明治薬科大学, 薬学部, 講師 (20386452)
石橋 賢一  明治薬科大学, 薬学部, 教授 (80223022)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsアクアポリン / 水代謝 / 尿濃縮 / エクソソーム / 腎臓 / バソプレシン / 膜輸送 / 水透過性 / 水チャネル / バイオマーカー / 水電解質
Outline of Final Research Achievements

Aquaporin-2 is water channel located in kidney collecting duct, and plays an essential role in urinary concentration. We clarified that 1) urine AQP2 is excreted in exosomes through endocytosis-MVB pathway, 2) disruption of exosome membrane is required for accurate measurement of urine AQP2 by ELISA, 3) urine AQP2 is an useful biomarker for clinical water metabolism disorders, 4) AQP2 in exosome preserves its original water channel function, 5) urinary excretion of AQP2 is responsive to vasopressin and shows long- and short-term regulations mediated by multiple phosphorylation of AQP2.

Academic Significance and Societal Importance of the Research Achievements

学術的にはエクソソームに存在する膜タンパクが本来の機能を保持していること示したことが注目される。エクソソームの生体での新しい役割が今後明らかになるだろう。
社会的にはAQP2の臨床応用に耐えるELISA測定法の確立は意義深い。今後臨床応用が進むことが期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities2018

    • Author(s)
      Miyazawa Yuko、Mikami Saki、Yamamoto Keiko、Sakai Masaki、Saito Tatsuya、Yamamoto Tadashi、Ishibashi Kenichi、Sasaki Sei
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 22 Issue: 4 Pages: 782-788

    • DOI

      10.1007/s10157-018-1538-6

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus2018

    • Author(s)
      Ando Fumiaki、Mori Shuichi、Yui Naofumi、Morimoto Tetsuji、Nomura Naohiro、Sohara Eisei、Rai Tatemitsu、Sasaki Sei、Kondo Yoshiaki、Kagechika Hiroyuki、Uchida Shinichi
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1411-1411

    • DOI

      10.1038/s41467-018-03771-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ser-261 phospho-regulation is involved in pS256 and pS269-mediated aquaporin-2 apical translocation2017

    • Author(s)
      Yui Naofumi、Ando Fumiaki、Sasaki Sei、Uchida Shinichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 490 Issue: 3 Pages: 1039-1044

    • DOI

      10.1016/j.bbrc.2017.06.162

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alkali treatment stabilizes fluctuations of urine AQP2 values measured by ELISA2016

    • Author(s)
      S. Sasaki, Y. Saijo, Y. Ohmoto, F. Iwata, D. Koga, K. Katsuragi
    • Journal Title

      ClinExpNephrol

      Volume: 20 Issue: 3 Pages: 450-455

    • DOI

      10.1007/s10157-015-1176-1

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disruption of Membranes of Extracellular Vesicles Is Necessary for ELISA Determination of Urine AQP2: Proof of Disruption and Epitopes of AQP2 Antibodies2016

    • Author(s)
      M. Nameta, Y. Saijo, Y. Ohmoto, K. Katsuragi, K. Yamamoto, T. Yamamoto, K. Ishibashi, S. Sasaki
    • Journal Title

      Int J Mol Sci

      Volume: 17 Issue: 10 Pages: 1634-1634

    • DOI

      10.3390/ijms17101634

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway.2016

    • Author(s)
      Ando F, Sohara E, Morimoto T, Yui N, Nomura N, Kikuchi E, Takahashi D, Mori T, Vandewalle A, Rai T, Sasaki S, Kondo Y, Uchida S.
    • Journal Title

      Nat Commun.

      Volume: 7 Issue: 1 Pages: 13636-13636

    • DOI

      10.1038/ncomms13636

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Urinary excretion of the water channel aquaporin 2 correlated with the pharmacological effect of tolvaptan in cirrhotic patients with ascites2016

    • Author(s)
      Nakanishi H, Kurosaki M, Hosokawa T, Takahashi Y, Itakura J, Suzuki S, Yasui Y, Tamaki N, Nakakuki N, Takada H, Higuchi M, Komiyama Y, Yoshida T, Takaura K, Hayashi T, Kuwabara K, Sasaki S, Izumi N
    • Journal Title

      Gastroenterol. 2015 Nov 26. [Epub ahead of print]

      Volume: 印刷中 Issue: 6 Pages: 620-627

    • DOI

      10.1007/s00535-015-1143-3

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Phosphorylation of Ser261 and dephosphorylation of Ser269 is important for urinary excretion of AQP2.2018

    • Author(s)
      Sasaki S, Sakai M, Mizumura H, Matsumoto T, Noda Y, Yui N, Ishibashi K.
    • Organizer
      51th Annual Meeting of American Society of Nephrology.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional and proteinous characterization of AQP2-rich extracellular vesicles in human urine.2017

    • Author(s)
      Mikami S, MiyazawaY, Sakai M, Saito T, Tanaka Y, Yamamoto K, Yamamoto T, Ishibashi K, Sasaki S
    • Organizer
      54th ERA-EDTA Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Proteomics and water channel function of AQP2-rich extracellular vesicles in human urine.2017

    • Author(s)
      MiyazawaY, Mikami S, Sakai M, Saito T, Ishibashi K, Sasaki S
    • Organizer
      50th Annual Meeting of American Society of Nephrology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 尿中AQP2の基礎的臨床的検討2017

    • Author(s)
      三上早紀、宮澤優子、斉藤達也、田中靖子、佐藤恵子、野田裕美、山本恵子、山本格、石橋賢一、佐々木成
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Urine AQP2 Comes from Exosome Pathway and Represents a Long-term Regulation of Vasopressin2016

    • Author(s)
      Sei Sasaki1, Yoko Saijo, Yasukazu Ohmoto, Kiyonori Katsuragi, Kenichi Ishibashi, Keiko Yamamoto, Tadashi Yamamoto
    • Organizer
      2016年アメリカ腎臓学会
    • Place of Presentation
      マコーミック会議場(シカゴ)
    • Year and Date
      2016-11-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 尿中AQP2排泄機序の基礎的検討:エクソソームとトラフィッキング2016

    • Author(s)
      酒井柾、高橋由衣、田中靖子、石橋賢一、佐々木成、 行田正晃、山本恵子、山本格
    • Organizer
      第59回日本腎臓学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-06-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Urine Aquaporin-2: Improvement in ELISA Measurements by alkali pre-treatment and mechanisms of the secretion2015

    • Author(s)
      Sei Sasaki, Saijo Y, Ohmoto Y, Iwata F, Koga D, Shimada T, Sakai M, Takahashi Y, Tanaka Y, Ishibashi K, Katsuragi K
    • Organizer
      アメリカ腎臓学会
    • Place of Presentation
      サンディエゴ (アメリカ)
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cross-talk between bedside and bench of AQP22015

    • Author(s)
      Sei Sasaki
    • Organizer
      Second World Congress on Water Channel Proteins
    • Place of Presentation
      クルジェナポカ (ルーマニア)
    • Year and Date
      2015-05-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 明治薬科大学病態生理学

    • URL

      https://www.my-pharm.ac.jp/education/kdb/lab/labo_3.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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