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Int J Biochem Cell Biol. 2014 Jul;52:174-9. doi: 10.1016/j.biocel.2014.02.006. Epub 2014 Feb 20.

Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

Author information

1
Department of Translational Pulmonology and Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany. Electronic address: Marcus.Mall@med.uni-heidelberg.de.
2
Department of Translational Pulmonology and Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.

Abstract

Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF.

KEYWORDS:

Airway surface dehydration; Cystic fibrosis; Early lung disease; Mouse model; Preventive therapy

PMID:
24561284
DOI:
10.1016/j.biocel.2014.02.006
[Indexed for MEDLINE]

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