作者
Marcus Mall, Barbara R Grubb, Jack R Harkema, Wanda K O'Neal, Richard C Boucher
发表日期
2004/5/1
期刊
Nature medicine
卷号
10
期号
5
页码范围
487-493
出版商
Nature Publishing Group US
简介
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 …
引用总数
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M Mall, BR Grubb, JR Harkema, WK O'Neal… - Nature medicine, 2004