Preconditioning effects of physiological cyclic stretch on pathologically mechanical stretch-induced alveolar epithelial cell apoptosis and barrier dysfunction
Preconditioning effects of physiological cyclic stretch on pathologically mechanical stretch-induced alveolar epithelial cell apoptosis and barrier dysfunction
复制标题
生理循环拉伸对病理机械拉伸诱导的肺泡上皮细胞凋亡和屏障功能障碍的预处理作用。
DOI：
10.1016/j.bbrc.2014.03.063
复制
发表时间：
2014-06-06
影响因子：
3.1
通讯作者：
Dai, Yan
中科院分区：
文献类型：
--
作者：
Gao, Ju;Huang, Tao;Dai, Yan
背景：我们的目的是研究生理循环拉伸预处理对病理性机械拉伸和屏障功能障碍诱导的肺泡上皮细胞凋亡的影响，以及这些影响如何与小GTPases Rac和Rho mRNA的差异表达相关。方法：肺泡上皮细胞分别接受5%和20%的循环拉伸（CS）处理。以正常细胞培养中维持的细胞为阴性对照。另一方面，比较和测量在病理性CS刺激（20% CS）处理6小时前，在不同持续时间（0、15、30、60和120 min）的CS生理相关强度（5% CS）预处理或不预处理的细胞中细胞凋亡和Rac/Rho活性。结果：病理性CS可引起细胞凋亡率显著升高，认为与Rac mRNA的抑制和Rho mRNA的激活有关。相比之下，生理5%-CS预处理抑制细胞凋亡，诱导几乎完全的单层恢复，肌动蛋白应激纤维减少，细胞旁间隙形成。与对细胞凋亡和上皮细胞完整性的差异效应一致，生理性CS预处理增强了Rac mRNA的表达，抑制了Rho的激活。结论：生理性CS预处理对细胞凋亡有抑制作用，同时通过调控Rac和Rho活性对上皮细胞恢复有刺激作用。(C) 2014年由Elsevier Inc.出版。
Background: We aim to investigate the effects of preconditioning of physiological cyclic stretch on the alveolar epithelial cell apoptosis induced by pathologically mechanical stretch and barrier dysfunction and how these effects are linked to differential expression of small GTPases Rac and Rho mRNA.Methods: Pulmonary alveolar epithelial cells were subjected to different treatments of cyclic stretch (CS) at 5% and 20% elongation, respectively. Cells maintained in normal cell culture were used as negative control. On the other hand, cell apoptosis and Rac/Rho activities in cells with or without preconditioning of physiologically relevant magnitudes of CS (5% CS) with different durations (0, 15, 30, 60 and 120 min) in prior to 6-h treatment with pathological CS stimulation (20% CS) were compared and measured.Results: Pathological CS could cause a significant increase in apoptosis rate, which is considered to be associated with the repression of Rac mRNA and activation of Rho mRNA. In contrast, physiological 5%-CS preconditioning suppressed cell apoptosis and induced nearly complete monolayer recovery with fewer actin stress fibers and paracellular gap formation. Consistent with differential effects on cell apoptosis and epithelial cell integrity, physiological CS preconditioning enhanced expression of Rac mRNA but inhibited Rho activation.Conclusions: Physiological CS preconditioning has an inhibitory effect on cell apoptosis while exerts a stimulatory impact on epithelial cell recovery via regulation of Rac and Rho activities. (C) 2014 Published by Elsevier Inc.