Airway surface liquid volume regulation determines different airway phenotypes in liddle compared with betaENaC-overexpressing mice.

Détails

Ressource 1Télécharger: Mall_2010 - copie.pdf (2422.74 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_44A5A1B88EA4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Airway surface liquid volume regulation determines different airway phenotypes in liddle compared with betaENaC-overexpressing mice.
Périodique
Journal of Biological Chemistry
Auteur(s)
Mall M.A., Button B., Johannesson B., Zhou Z., Livraghi A., Caldwell R.A., Schubert S.C., Schultz C., O'Neal W.K., Pradervand S., Hummler E., Rossier B.C., Grubb B.R., Boucher R.C.
ISSN
1083-351X
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
285
Numéro
35
Pages
26945-26955
Langue
anglais
Résumé
Studies in cystic fibrosis patients and mice overexpressing the epithelial Na(+) channel beta-subunit (betaENaC-Tg) suggest that raised airway Na(+) transport and airway surface liquid (ASL) depletion are central to the pathogenesis of cystic fibrosis lung disease. However, patients or mice with Liddle gain-of-function betaENaC mutations exhibit hypertension but no lung disease. To investigate this apparent paradox, we compared the airway phenotype (nasal versus tracheal) of Liddle with CFTR-null, betaENaC-Tg, and double mutant mice. In mouse nasal epithelium, the region that functionally mimics human airways, high levels of CFTR expression inhibited Liddle epithelial Nat channel (ENaC) hyperfunction. Conversely, in mouse trachea, low levels of CFTR failed to suppress Liddle ENaC hyperfunction. Indeed, Na(+) transport measured in Ussing chambers ("flooded" conditions) was raised in both Liddle and betaENaC-Tg mice. Because enhanced Na(+) transport did not correlate with lung disease in these mutant mice, measurements in tracheal cultures under physiologic "thin film" conditions and in vivo were performed. Regulation of ASL volume and ENaC-mediated Na(+) absorption were intact in Liddle but defective in betaENaC-Tg mice. We conclude that the capacity to regulate Na(+) transport and ASL volume, not absolute Na(+) transport rates in Ussing chambers, is the key physiologic function protecting airways from dehydration-induced lung disease.
Mots-clé
Animals, Cystic Fibrosis/metabolism, Cystic Fibrosis/pathology, Cystic Fibrosis Transmembrane Conductance Regulator/genetics, Cystic Fibrosis Transmembrane Conductance Regulator/metabolism, Epithelial Sodium Channel/biosynthesis, Epithelial Sodium Channel/genetics, Gene Expression Regulation, Humans, Ion Transport/genetics, Liddle Syndrome/metabolism, Liddle Syndrome/pathology, Mice, Mice, Knockout, Mutation, Nasal Mucosa/metabolism, Nasal Mucosa/pathology, Organ Culture Techniques, Sodium/metabolism, Trachea/metabolism, Trachea/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/03/2011 15:47
Dernière modification de la notice
20/08/2019 13:49
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