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Mechanisms of cellular and intercellular coordination of sodium transport in renal collecting duct principal cells

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Defense Thèse de doctorat : Univ. Genève, 2014 - Sc. 4671 - 2014/04/15
Abstract This study was aimed at dissecting mechanisms of coordination between ENaC and Na,K-ATPase as well as between transcellular Na+ transport and paracellular permeability in renal collecting duct principal cells. Aldosterone-clamped rats fed of varying Na+ intake and mCCDcl1 cells that overexpress γ-ENaC in a doxycycline-inducible manner were used. Crosstalk between ENaC and Na,K-ATPase was observed in vivo and in vitro. Increased apical Na+ entry was invariably associated with increased basolateral Na+ extrusion via Na,K-ATPase. This was accounted for by decreased endocytosis and degradation of cell-surface Na,K-ATPase, which was mediated by inhibition of p38 kinase activity. Crosstalk between transcellular Na+ transport and paracellular permeability was also observed in cultured mCCDcl1 cells. Increased transcellular Na+ transport was associated with decreased paracellular permeability as inferred by increased transepithelial resistance. This effect was mediated by decreased β-catenin signaling through the release of its transcriptional suppression of claudin-8 in response to increased transcellular Na+ transport.
Keywords Collecting ductPrincipal cellsENaCNaK-ATPaseTight junctionP38 kinaseβ-cateninClaudin-8
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URN: urn:nbn:ch:unige-369314
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Research group Groupe Eric Féraille (néphrologie) (29)
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WANG, Yubao. Mechanisms of cellular and intercellular coordination of sodium transport in renal collecting duct principal cells. Université de Genève. Thèse, 2014. https://archive-ouverte.unige.ch/unige:36931

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Deposited on : 2014-05-26

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