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- Title
Transepithelial ion transport is suppressed in hypoxic sinonasal epithelium.
- Authors
Blount, Angela; Zhang, Shaoyan; Chestnut, Michael; Hixon, Brian; Skinner, Daniel; Sorscher, Eric J.; Woodworth, Bradford A.
- Abstract
Objectives/Hypothesis: Sinonasal respiratory epithelial mucociliary clearance is dependent on the transepithelial transport of ions such as Cl−. The objectives of the present study were to investigate the role of oxygen restriction in 1) Cl− transport across primary sinonasal epithelial monolayers, 2) expression of the apical Cl− channels cystic fibrosis transmembrane conductance regulator (CFTR) and transmembrane protein 16A (TMEM16A), and 3) the pathogenesis of chronic rhinosinusitis. Study Design: In vitro investigation. Methods: Murine nasal septal epithelial (MNSE), wild type, and human sinonasal epithelial (HSNE) cultures were incubated under hypoxic conditions (1% O2, 5% CO2). Cultures were mounted in Ussing chambers for ion transport measurements. CFTR and TMEM16A expression were measured using quantitative reverse-transcription polymerase chain reaction (RT-PCR). Results: The change in short-circuit current (ΔISC in microamperes per square centimeter) attributable to CFTR (forskolin-stimulated) was significantly decreased due to a 12-hour hypoxia exposure in both MNSE (13.55 ± 0.46 vs. 19.23 ± 0.18) and HSNE (19.55 ± 0.56 vs. 25.49 ± 1.48 [control]; P < .05). TMEM16A (uridine triphosphate-stimulated transport) was inhibited by 48 hours of hypoxic exposure in MNSE (15.92 ± 2.87 vs. 51.44 ± 3.71 [control]; P < .05) and by 12 hours of hypoxic exposure in HSNE (16.75 ± 0.68 vs. 24.15 ± 1.35 [control]). Quantitative RT-PCR (reported as relative mRNA levels ± standard deviation) demonstrated significant reductions in both CFTR and TMEM16A mRNA expression in MNSE and HSNE owing to airway epithelial hypoxia. Conclusions: Sinonasal epithelial CFTR and TMEM16A-mediated Cl− transport and mRNA expression were robustly decreased in an oxygen-restricted environment. These findings indicate that persistent hypoxia may lead to acquired defects in sinonasal Cl− transport in a fashion likely to confer mucociliary dysfunction in chronic rhinosinusitis.
- Subjects
PARANASAL sinuses; CALCIUM-dependent potassium channels; SINUSITIS; HYPOXEMIA; MURINE sarcoma viruses; NASAL mucosa; EPITHELIUM; MUCOCILIARY system; DISEASES
- Publication
Laryngoscope, 2011, Vol 121, Issue 9, p1929
- ISSN
0023-852X
- Publication type
Article
- DOI
10.1002/lary.21921