ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.

Détails

Ressource 1Télécharger: Planès_EMM_Dec - copie.pdf (880.98 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_B5618048ACCE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.
Périodique
EMBO Molecular Medicine
Auteur(s)
Planès C., Randrianarison N.H., Charles R.P., Frateschi S., Cluzeaud F., Vuagniaux G., Soler P., Clerici C., Rossier B.C., Hummler E.
ISSN
1757-4684
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
2
Numéro
1
Pages
26-37
Langue
anglais
Résumé
Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance.
Mots-clé
Adrenergic beta-Agonists/pharmacology, Animals, Cells, Cultured, Epithelial Cells/metabolism, Epithelial Sodium Channel/genetics, Epithelial Sodium Channel/metabolism, Extravascular Lung Water/metabolism, Gene Deletion, Gene Expression, Lung/metabolism, Mice, Pulmonary Alveoli/cytology, Pulmonary Alveoli/metabolism, Pulmonary Edema/metabolism, Respiratory Mucosa/metabolism, Serine Endopeptidases/genetics, Serine Endopeptidases/metabolism, Water-Electrolyte Balance/drug effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/01/2010 17:27
Dernière modification de la notice
20/08/2019 15:23
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