McCullough Morgan, Joshi Ilin V, Pereira Nicolas L, Fuentes Nathalie, Krishnan Ramaswamy, Druey Kirk M
Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, USA.
Center for Vascular Biology Research, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Boston, Massachusetts, USA.
J Biol Chem. 2025 Jan;301(1):108028. doi: 10.1016/j.jbc.2024.108028. Epub 2024 Nov 28.
To contract, to deform, and remodel, the airway smooth muscle cell relies on dynamic changes in the structure of its mechanical force-bearing cytoskeleton. These alternate between a "fluid-like" (relaxed) state characterized by weak contractile protein-protein interactions within the cytoskeletal apparatus and a "solid-like" (contractile) state promoted by strong and highly organized molecular interactions. In this review, we discuss the roles for actin, myosin, factors promoting actin polymerization and depolymerization, adhesome complexes, and cell-cell junctions in these dynamic processes. We describe the relationship between these cytoskeletal factors, extracellular matrix components of bronchial tissue, and mechanical stretch and other changes within the airway wall in the context of the physical mechanisms of cytoskeletal fluidization-resolidification. We also highlight studies that emphasize the distinct processes of cell shortening and force transmission in airway smooth muscle and previously unrecognized roles for actin in cytoskeletal dynamics. Finally, we discuss the implications of these discoveries for understanding and treating airway obstruction in asthma.
为了收缩、变形和重塑，气道平滑肌细胞依赖于其承载机械力的细胞骨架结构的动态变化。这些变化在细胞骨架装置内由弱收缩性蛋白质 - 蛋白质相互作用所表征的“流体样”（松弛）状态和由强且高度组织化的分子相互作用所促进的“固体样”（收缩）状态之间交替。在本综述中，我们讨论了肌动蛋白、肌球蛋白、促进肌动蛋白聚合和解聚的因子、黏附体复合物以及细胞间连接在这些动态过程中的作用。我们在细胞骨架流化 - 再固化的物理机制背景下，描述了这些细胞骨架因子、支气管组织的细胞外基质成分、气道壁内的机械拉伸及其他变化之间的关系。我们还强调了一些研究，这些研究强调了气道平滑肌中细胞缩短和力传递的不同过程以及肌动蛋白在细胞骨架动力学中以前未被认识到的作用。最后，我们讨论了这些发现对理解和治疗哮喘气道阻塞的意义。
