Cyclic compression increases F508 Del CFTR expression in ciliated human airway epithelium

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 317; no. 2; pp. L247 - L258
• Main Authors: Marozkina, Nadzeya, Bosch, Jürgen, Cotton, Calvin, Smith, Laura, Seckler, James, Zaman, Khalequz, Rehman, Shagufta, Periasamy, Ammasi, Gaston, Herbert, Altawallbeh, Ghaith, Davis, Michael, Jones, David R., Schilz, Robert, Randell, Scott H., Gaston, Benjamin
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2019
• Subjects: Calcium influx; Calcium ions; Cell Line; Cilia; Compression; Cystic fibrosis; Cystic Fibrosis - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Epithelium - metabolism; Humans; Lung - metabolism; Lungs; Maturation; Nitrogen oxides; Oxides; Photochemicals; Pressure; Proteins; Respiratory Mucosa - metabolism; Respiratory tract; airway pressure; airway clearance; cystic fibrosis; nitrosocysteine; airway cilia
• ISSN: 1040-0605; 1522-1504; 1522-1504
• DOI: 10.1152/ajplung.00020.2019

The mechanisms by which transepithelial pressure changes observed during exercise and airway clearance can benefit lung health are challenging to study. Here, we have studied 117 mature, fully ciliated airway epithelial cell filters grown at air-liquid interface grown from 10 cystic fibrosis (CF) and 19 control subjects. These were exposed to cyclic increases in apical air pressure of 15 cmH 2 O for varying times. We measured the effect on proteins relevant to lung health, with a focus on the CF transmembrane regulator (CFTR). Immunoflourescence and immunoblot data were concordant in demonstrating that air pressure increased F508Del CFTR expression and maturation. This effect was in part dependent on the presence of cilia, on Ca 2+ influx, and on formation of nitrogen oxides. These data provide a mechanosensory mechanism by which changes in luminal air pressure, like those observed during exercise and airway clearance, can affect epithelial protein expression and benefit patients with diseases of the airways.