Journal article
Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance
American Journal of Respiratory Cell and Molecular Biology (Online), Vol.54(4), pp.469-481
04/01/2016
DOI: 10.1165/rcmb.2015-0090OC
PMCID: PMC4821051
PMID: 26334941
Abstract
Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel lead to viscous secretions from submucosal glands that cannot be properly hydrated and cleared by beating cilia in cystic fibrosis (CF) airways. The authors used a proteomics approach to characterize the proteins contained in CF and non-CF submucosal gland fluid droplets and found that differentially regulated proteases (cathepsin S and H) and their antiprotease (cystatin C) influenced the equilibration of fluid on the airway surface and tracheal mucociliary clearance (MCC). Contrary to prevailing models of airway hydration and clearance, cystatin C, or raising the airway surface liquid (ASL) pH, inhibited catheps-independent ENaC-mediated fluid absorption and raised the height of ASL, and yet decreased MCC velocity. Importantly, coupling of both CFTR and ENaC activities were required for effective MCC and for effective ASL height equilibration after volume challenge. The findings demonstrate that, after volume challenge, pH-dependent protease-mediated coupling of CFTR and ENaC activities are required for rapid fluid equilibration at the airway surface and for effective MCC.
Details
- Title: Subtitle
- Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance
- Creators
- T Idil Apak Evans - University of Iowa, Anatomy and Cell BiologyNam Soo JooNicholas W KeiserZiying Yan - University of Iowa, Anatomy and Cell BiologyScott R Tyler - University of Iowa, Anatomy and Cell BiologyWeiliang XieYulong Zhang - University of Iowa, Anatomy and Cell BiologyJordy J HsiaoHyung-Ju ChoMichael E Wright - University of Iowa, Molecular Physiology and BiophysicsJeffrey J WineJohn F Engelhardt - University of Iowa, Anatomy and Cell Biology
- Resource Type
- Journal article
- Publication Details
- American Journal of Respiratory Cell and Molecular Biology (Online), Vol.54(4), pp.469-481
- Publisher
- American Thoracic Society; New York
- DOI
- 10.1165/rcmb.2015-0090OC
- PMID
- 26334941
- PMCID
- PMC4821051
- ISSN
- 1535-4989
- eISSN
- 1535-4989
- Language
- English
- Date published
- 04/01/2016
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9983759099902771
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