黏膜炎症期间肌动蛋白细胞骨架动力学：来自破损上皮屏障的视角
Actin cytoskeleton dynamics during mucosal inflammation: a view from broken epithelial barriers.
作者信息
Lechuga Susana, Ivanov Andrei I
机构信息
Department of Inflammation and Immunity, Lerner Research Institute of Cleveland Clinic Foundation, Cleveland, OH 44195.
出版信息
Curr Opin Physiol. 2021 Feb;19:10-16. doi: 10.1016/j.cophys.2020.06.012. Epub 2020 Jun 30.
Abstract
Disruption of epithelial barriers is a key pathogenic event of mucosal inflammation: It ignites the exaggerated immune response and accelerates tissue damage. Loss of barrier function is attributed to the abnormal structure and permeability of epithelial adherens junctions and tight junctions, driven by inflammatory stimuli through a variety of cellular mechanisms. This review focuses on roles of the actin cytoskeleton in mediating disruption of epithelial junctions and creation of leaky barriers in inflamed tissues. We summarize recent advances in understanding the role of cytoskeletal remodeling driven by actin filament turnover and myosin II-dependent contractility in the homeostatic regulation of epithelial barriers and barrier disruption during mucosal inflammation. We also discuss how the altered biochemical and physical environment of the inflamed tissues could affect the dynamics of the junction-associated actomyosin cytoskeleton, leading to the disruption of epithelial barriers.
摘要
上皮屏障的破坏是黏膜炎症的关键致病事件
它引发过度的免疫反应并加速组织损伤。屏障功能的丧失归因于上皮黏附连接和紧密连接的结构异常及通透性增加，这是由炎症刺激通过多种细胞机制驱动的。本综述聚焦于肌动蛋白细胞骨架在介导上皮连接破坏以及在炎症组织中形成渗漏屏障方面的作用。我们总结了在理解由肌动蛋白丝周转和肌球蛋白II依赖性收缩驱动的细胞骨架重塑在黏膜炎症期间上皮屏障的稳态调节和屏障破坏中的作用方面的最新进展。我们还讨论了炎症组织中改变的生化和物理环境如何影响与连接相关的肌动球蛋白细胞骨架的动态变化，从而导致上皮屏障的破坏。
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2
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3
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