Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center 4B.64, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Am J Respir Cell Mol Biol. 2011 Jul;45(1):120-6. doi: 10.1165/rcmb.2010-0235OC. Epub 2010 Sep 24.
Epithelial cells have the ability to regulate paracellular permeability dynamically in response to extracellular stimuli. With every respiratory effort, airway epithelial cells are exposed to both physiologic as well as pathologic stimuli, and regulation of the epithelial barrier in response to these stimuli is crucial to respiratory function. We report that increased membrane septin-2 localization mediates decreases in paracellular permeability by altering cortical actin arrangement in human airway epithelial cells. This phenomenon occurs in response to both physiologic levels of shear stress and a pathologic stimulus, particular matter exposure. The resulting changes in barrier function in response to septin-2 redistribution have a significant impact on the ability of the apical ligand, epidermal growth factor, to interact with its receptor, epidermal growth factor receptor, which is segregated to the basolateral side in airway epithelial cells. This suggests that the dynamic regulation of the epithelial barrier function is essential in regulating signaling responses to extracellular stimuli. These findings indicate that septin-2 plays a fundamental role in regulating barrier function by altering cortical actin expression.
上皮细胞具有根据细胞外刺激动态调节细胞旁通透性的能力。在每一次呼吸中，气道上皮细胞都会受到生理和病理刺激的影响，因此，上皮屏障对这些刺激的调节对于呼吸功能至关重要。我们报告称，膜 septin-2 定位的增加通过改变人呼吸道上皮细胞皮质肌动蛋白排列来介导细胞旁通透性的降低。这种现象既发生在生理水平的切应力下，也发生在病理刺激，特别是颗粒物暴露下。这种 septin-2 重分布引起的屏障功能变化对顶端配体表皮生长因子与其受体表皮生长因子受体相互作用的能力有显著影响，表皮生长因子受体在气道上皮细胞中被隔离到基底外侧。这表明，上皮屏障功能的动态调节对于调节细胞外刺激的信号反应至关重要。这些发现表明，septin-2 通过改变皮质肌动蛋白的表达来发挥调节屏障功能的基本作用。
