Length-Dependent Modulation of Cytoskeletal Remodeling and Mechanical Energetics in Airway Smooth Muscle
Length-Dependent Modulation of Cytoskeletal Remodeling and Mechanical Energetics in Airway Smooth Muscle
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DOI：
10.1165/rcmb.2010-0144oc
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发表时间：
2011-06-01
影响因子：
6.4
通讯作者：
Hai, Chi-Ming
中科院分区：
文献类型：
--
作者：
Kim, Hak Rim;Liu, Katrina;Hai, Chi-Ming
肌动蛋白细胞骨架重构是气道平滑肌收缩的重要机制。我们测试的假设，机械应变调节胆碱能受体介导的肌动蛋白结合和整合素结合蛋白在完整的气道平滑肌细胞骨架招聘，从而调节气道平滑肌的机械能。我们发现，卡巴胆碱刺激的肌动蛋白相关蛋白-3（Arp 3），后黏着斑蛋白和talin的细胞骨架招募在短肌肉长度上调，在长肌肉长度下调，这表明肌动蛋白cytokeron-integrin复合物在缩短的ASM中富含交联和分支的肌动蛋白丝。正弦长度振荡过程中的机械能输出/输入比取决于肌肉长度、振荡幅度和胆碱能激活。胆碱能刺激对短肌和长肌机械能输出/输入比的增强作用可以分别通过细胞骨架募集和横桥循环的长度依赖性调制来解释。我们假设ASM作为一种混合生物材料，能够在短肌肉长度下作为基于细胞分裂素的机械能储存器操作与长肌肉长度下作为肌动球蛋白驱动的机械能发生器操作之间切换。这一假设预测，靶向参与细胞骨架募集的信号分子可能提供一种新的方法来扩张阻塞性气道疾病中塌陷的气道。
Actin cytoskeletal remodeling is an important mechanism of airway smooth muscle (ASM) contraction. We tested the hypothesis that mechanical strain modulates the cholinergic receptor-mediated cytoskeletal recruitment of actin-binding and integrin-binding proteins in intact airway smooth muscle, thereby regulating the mechanical energetics of airway smooth muscle. We found that the carbachol-stimulated cytoskeletal recruitment of actin-related protein-3 (Arp3), metavinculin, and talin were up-regulated at short muscle lengths and down-regulated at long muscle lengths, suggesting that the actin cytoskeleton-integrin complex becomes enriched in cross-linked and branched actin filaments in shortened ASM. The mechanical energy output/input ratio during sinusoidal length oscillation was dependent on muscle length, oscillatory amplitude, and cholinergic activation. The enhancing effect of cholinergic stimulation on mechanical energy output/input ratio at short and long muscle lengths may be explained by the length-dependent modulation of cytoskeletal recruitment and crossbridge cycling, respectively. We postulate that ASM functions as a hybrid biomaterial, capable of switching between operating as a cytoskeleton-based mechanical energy store at short muscle lengths to operating as an actomyosin-powered mechanical energy generator at long muscle lengths. This postulate predicts that targeting the signaling molecules involved in cytoskeletal recruitment may provide a novel approach to dilating collapsed airways in obstructive airway disease.