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首页> 外文期刊>The Laryngoscope: A Medical Journal for Clinical and Research Contributions in Otolaryngology, Head and Neck Medicine and Surgery, Facial Plastic and Reconstructive Surgery .. >Transepithelial ion transport is suppressed in hypoxic sinonasal epithelium.
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Transepithelial ion transport is suppressed in hypoxic sinonasal epithelium.

机译：缺氧鼻窦上皮中的上皮离子运输受到抑制。

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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% O(2) , 5% CO(2) ). 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 (DeltaI(SC) 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.
机译：目的/假设：鼻腔呼吸道上皮粘膜纤毛清除取决于离子如Cl（-）的经上皮运输。本研究的目的是研究氧限制在1）Cl（-）跨初级鼻窦上皮单层运输中的作用，2）顶端Cl（-）通道的表达囊性纤维化跨膜电导调节剂（CFTR）和跨膜蛋白16A（TMEM16A），和3）慢性鼻鼻窦炎的发病机理。研究设计：体外研究。方法：小鼠鼻中隔上皮（MNSE），野生型和人类鼻窦上皮（HSNE）培养物在低氧条件下（1％O（2），5％CO（2））孵育。将培养物安装在Usssing室中进行离子迁移测量。使用定量逆转录聚合酶链反应（RT-PCR）测量CFTR和TMEM16A表达。结果：由于两个MNSE均暴露了12小时的缺氧，CFTR（受毛喉素刺激）引起的短路电流（DeltaI（SC）以每平方厘米微安每平方厘米为单位）的变化显着降低（13.55 +/- 0.46vs。 19.23 +/- 0.18）和HSNE（19.55 +/- 0.56与25.49 +/- 1.48 [对照]; P <.05）。在MNSE中低氧暴露48小时（15.92 +/- 2.87对51.44 +/- 3.71 [对照组]; P <.05）和在HSNE中低氧暴露12小时（TMEM16A）（三磷酸尿苷刺激运输）被抑制。 16.75 +/- 0.68与24.15 +/- 1.35 [对照]）。定量RT-PCR（报告为相对mRNA水平+/-标准偏差）显示由于气道上皮低氧，MNSE和HSNE中CFTR和TMEM16A mRNA表达均显着降低。结论：在氧气受限的环境中，鼻上皮CFTR和TMEM16A介导的Cl（-）转运和mRNA表达被强烈降低。这些发现表明持续性的缺氧可能导致慢性鼻-鼻窦炎的黏膜纤毛功能障碍，从而导致鼻窦Cl（-）转运获得性缺陷。

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