Departments of Animal Science, Integrative Biology and Physiology, University of Minnesota , St. Paul, Minnesota.
Am J Physiol Cell Physiol. 2019 Jan 1;316(1):C16-C32. doi: 10.1152/ajpcell.00341.2018. Epub 2018 Oct 10.
Mucociliary clearance is critically important in protecting the airways from infection and from the harmful effects of smoke and various inspired substances known to induce oxidative stress and persistent inflammation. An essential feature of the clearance mechanism involves regulation of the periciliary liquid layer on the surface of the airway epithelium, which is necessary for normal ciliary beating and maintenance of mucus hydration. The underlying ion transport processes associated with airway surface hydration include epithelial Na channel-dependent Na absorption occurring in parallel with CFTR and Ca-activated Cl channel-dependent anion secretion, which are coordinately regulated to control the depth of the periciliary liquid layer. Oxidative stress is known to cause both acute and chronic effects on airway ion transport function, and an increasing number of studies in the past few years have identified an important role for autophagy as part of the physiological response to the damaging effects of oxidation. In this review, recent studies addressing the influence of oxidative stress and autophagy on airway ion transport pathways, along with results showing the potential of autophagy modulators in restoring the function of ion channels involved in transepithelial electrolyte transport necessary for effective mucociliary clearance, are presented.
黏液纤毛清除对于保护气道免受感染以及烟雾和各种已知能诱导氧化应激和持续炎症的吸入物质的有害影响至关重要。清除机制的一个基本特征涉及气道上皮表面纤毛周围液体层的调节，这对于正常纤毛摆动和维持黏液水合是必需的。与气道表面水合相关的潜在离子转运过程包括上皮钠通道依赖性 Na 吸收，与 CFTR 和钙激活 Cl 通道依赖性阴离子分泌平行发生，它们被协调调节以控制纤毛周围液体层的深度。氧化应激已知会对气道离子转运功能产生急性和慢性影响，过去几年的越来越多的研究已经确定自噬作为对氧化损伤的生理反应的一部分的重要作用。在这篇综述中，介绍了最近的研究，这些研究涉及氧化应激和自噬对气道离子转运途径的影响，以及自噬调节剂在恢复参与跨上皮电解质转运的离子通道功能方面的潜力，这些离子通道对于有效的黏液纤毛清除是必需的。
