膜黏附连接调控气道平滑肌表型和功能。
Membrane adhesion junctions regulate airway smooth muscle phenotype and function.
机构信息
Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, Indiana, United States.
出版信息
Physiol Rev. 2023 Jul 1;103(3):2321-2347. doi: 10.1152/physrev.00020.2022. Epub 2023 Feb 16.
The local environment surrounding airway smooth muscle (ASM) cells has profound effects on the physiological and phenotypic properties of ASM tissues. ASM is continually subjected to the mechanical forces generated during breathing and to the constituents of its surrounding extracellular milieu. The smooth muscle cells within the airways continually modulate their properties to adapt to these changing environmental influences. Smooth muscle cells connect to the extracellular cell matrix (ECM) at membrane adhesion junctions that provide mechanical coupling between smooth muscle cells within the tissue. Membrane adhesion junctions also sense local environmental signals and transduce them to cytoplasmic and nuclear signaling pathways in the ASM cell. Adhesion junctions are composed of clusters of transmembrane integrin proteins that bind to ECM proteins outside the cell and to large multiprotein complexes in the submembranous cytoplasm. Physiological conditions and stimuli from the surrounding ECM are sensed by integrin proteins and transduced by submembranous adhesion complexes to signaling pathways to the cytoskeleton and nucleus. The transmission of information between the local environment of the cells and intracellular processes enables ASM cells to rapidly adapt their physiological properties to modulating influences in their extracellular environment: mechanical and physical forces that impinge on the cell, ECM constituents, local mediators, and metabolites. The structure and molecular organization of adhesion junction complexes and the actin cytoskeleton are dynamic and constantly changing in response to environmental influences. The ability of ASM to rapidly accommodate to the ever-changing conditions and fluctuating physical forces within its local environment is essential for its normal physiological function.
气道平滑肌 (ASM) 细胞周围的局部环境对 ASM 组织的生理和表型特性有深远的影响。ASM 不断受到呼吸过程中产生的机械力以及周围细胞外环境成分的影响。气道中的平滑肌细胞不断调节其特性以适应这些不断变化的环境影响。平滑肌细胞通过细胞膜黏附连接与细胞外基质 (ECM) 相连,这些连接为组织内的平滑肌细胞提供机械耦联。细胞膜黏附连接还能感知局部环境信号,并将其转导至 ASM 细胞的细胞质和核信号通路中。黏附连接由簇状跨膜整合素蛋白组成,这些蛋白与细胞外的 ECM 蛋白结合,并与细胞质下的大型多蛋白复合物结合。生理条件和来自周围 ECM 的刺激由整合素蛋白感知,并通过细胞质下黏附复合物转导至细胞骨架和核的信号通路。细胞局部环境与细胞内过程之间的信息传递使 ASM 细胞能够迅速适应其生理特性,以适应其细胞外环境中的调节影响:作用于细胞的机械和物理力、ECM 成分、局部介质和代谢物。黏附连接复合物和肌动蛋白细胞骨架的结构和分子组织是动态的,并根据环境影响不断变化。ASM 迅速适应其局部环境中不断变化的条件和波动的物理力的能力对于其正常的生理功能至关重要。