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Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway

Author

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  • Fumiaki Ando

    (Tokyo Medical and Dental University)

  • Eisei Sohara

    (Tokyo Medical and Dental University)

  • Tetsuji Morimoto

    (Tohoku Medical and Pharmaceutical University)

  • Naofumi Yui

    (Tokyo Medical and Dental University)

  • Naohiro Nomura

    (Tokyo Medical and Dental University)

  • Eriko Kikuchi

    (Tokyo Medical and Dental University)

  • Daiei Takahashi

    (Tokyo Medical and Dental University)

  • Takayasu Mori

    (Tokyo Medical and Dental University)

  • Alain Vandewalle

    (Centre de Recherche sur l’Inflammation (CRI), UMRS 1149)

  • Tatemitsu Rai

    (Tokyo Medical and Dental University)

  • Sei Sasaki

    (Tokyo Medical and Dental University)

  • Yoshiaki Kondo

    (Nihon University School of Medicine)

  • Shinichi Uchida

    (Tokyo Medical and Dental University)

Abstract

Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway. Wnt5a successfully increases the apical membrane localization of AQP2 and urine osmolality in an NDI mouse model. We also demonstrate that calcineurin is a key regulator of Wnt5a-induced AQP2 activation without affecting intracellular cAMP level and PKA activity. The importance of calcineurin is further confirmed with its activator, arachidonic acid, which shows vasopressin-like effects underlining that calcineurin activators may be potential therapeutic targets for heritable NDI.

Suggested Citation

  • Fumiaki Ando & Eisei Sohara & Tetsuji Morimoto & Naofumi Yui & Naohiro Nomura & Eriko Kikuchi & Daiei Takahashi & Takayasu Mori & Alain Vandewalle & Tatemitsu Rai & Sei Sasaki & Yoshiaki Kondo & Shini, 2016. "Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13636
    DOI: 10.1038/ncomms13636
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    Cited by:

    1. Wakana Shoda & Naohiro Nomura & Fumiaki Ando & Hideaki Tagashira & Takahiro Iwamoto & Akihito Ohta & Kiyoshi Isobe & Takayasu Mori & Koichiro Susa & Eisei Sohara & Tatemitsu Rai & Shinichi Uchida, 2020. "Sodium–calcium exchanger 1 is the key molecule for urinary potassium excretion against acute hyperkalemia," PLOS ONE, Public Library of Science, vol. 15(6), pages 1-23, June.

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