Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America.
PLoS One. 2014 Apr 16;9(4):e94828. doi: 10.1371/journal.pone.0094828. eCollection 2014.
Recent reports suggest that tidal stretches do not cause significant and sustainable dilation of constricted intact airways ex vivo. To better understand the underlying mechanisms, we aimed to map the physiological stretch-induced molecular changes related to cytoskeletal (CSK) structure and contractile force generation through integrin receptors. Using ultrasound, we measured airway constriction in isolated intact airways during 90 minutes of static transmural pressure (Ptm) of 7.5 cmH2O or dynamic variations between Ptm of 5 and 10 cmH20 mimicking breathing. Integrin and focal adhesion kinase activity increased during Ptm oscillations which was further amplified during constriction. While Ptm oscillations reduced β-actin and F-actin formation implying lower CSK stiffness, it did not affect tubulin. However, constriction was amplified when the microtubule structure was disassembled. Without constriction, α-smooth muscle actin (ASMA) level was higher and smooth muscle myosin heavy chain 2 was lower during Ptm oscillations. Alternatively, during constriction, overall molecular motor activity was enhanced by Ptm oscillations, but ASMA level became lower. Thus, ASMA and motor protein levels change in opposite directions due to stretch and contraction maintaining similar airway constriction levels during static and dynamic Ptm. We conclude that physiological Ptm variations affect cellular processes in intact airways with constriction determined by the balance among contractile and CSK molecules and structure.
最近的报告表明，潮汐拉伸不会导致受限制的完整气道在体外显著和可持续扩张。为了更好地理解潜在的机制，我们旨在通过整合素受体绘制与细胞骨架 (CSK) 结构和收缩力产生相关的生理拉伸诱导的分子变化图谱。我们使用超声测量了在 7.5 cmH2O 的静态跨壁压 (Ptm) 或模拟呼吸的 5 至 10 cmH20 的动态 Ptm 变化期间分离的完整气道中的气道收缩。整合素和粘着斑激酶活性在 Ptm 振荡期间增加，在收缩期间进一步放大。虽然 Ptm 振荡减少了 β-肌动蛋白和 F-肌动蛋白的形成，暗示 CSK 刚性降低，但它不影响微管蛋白。然而，当微管结构解体时，收缩被放大。在没有收缩的情况下，α-平滑肌肌动蛋白 (ASMA) 水平在 Ptm 振荡期间更高，平滑肌肌球蛋白重链 2 更低。相反，在收缩期间，Ptm 振荡增强了整体分子马达活性，但 ASMA 水平降低。因此，由于拉伸和收缩，ASMA 和运动蛋白水平以相反的方向变化，在静态和动态 Ptm 期间保持相似的气道收缩水平。我们得出结论，生理 Ptm 变化会影响完整气道中的细胞过程，而收缩由收缩和 CSK 分子和结构之间的平衡决定。
