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Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice.

Nature medicine | May 3, 2004

http://www.ncbi.nlm.nih.gov/pubmed/15077107

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective epithelial cAMP-dependent Cl(-) secretion and increased airway Na(+) absorption. The mechanistic links between these altered ion transport processes and the pathogenesis of cystic fibrosis lung disease, however, are unclear. To test the hypothesis that accelerated Na(+) transport alone can produce cystic fibrosis-like lung disease, we generated mice with airway-specific overexpression of epithelial Na(+) channels (ENaC). Here we show that increased airway Na(+) absorption in vivo caused airway surface liquid (ASL) volume depletion, increased mucus concentration, delayed mucus transport and mucus adhesion to airway surfaces. Defective mucus transport caused a severe spontaneous lung disease sharing features with cystic fibrosis, including mucus obstruction, goblet cell metaplasia, neutrophilic inflammation and poor bacterial clearance. We conclude that increasing airway Na(+) absorption initiates cystic fibrosis-like lung disease and produces a model for the study of the pathogenesis and therapy of this disease.

Pubmed ID: 15077107 RIS Download

Mesh terms: Animals | Cystic Fibrosis | Cystic Fibrosis Transmembrane Conductance Regulator | Disease Models, Animal | Epithelial Sodium Channels | Epithelium | Humans | Lung | Mice | Mice, Inbred C3H | Mice, Inbred C57BL | Mice, Transgenic | Mucus | Sodium | Sodium Channels

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