Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing
Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing
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DOI：
10.1152/ajplung.00371.2010
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发表时间：
2011-10-01
影响因子：
4.9
通讯作者：
Waters, Christopher M.
中科院分区：
文献类型：
--
作者：
Crosby, Lynn M.;Luellen, Charlean;Waters, Christopher M.
克罗斯比 LM、卢埃伦 C、张 Z、塔格 LL、辛克莱 SE、沃特斯 CM。 II 型肺泡上皮细胞的生死平衡：增殖、凋亡以及循环拉伸对伤口愈合的影响。 Am J Physiol Lung Cell Mol Physiol 301：L536-L546，2011。首次发表于 2011 年 7 月 1 日； doi: 10.1152/ajplung.00371.2010.-急性肺损伤后，肺泡上皮的修复发生在经历循环机械变形的基底上。虽然之前的研究表明机械拉伸会增加肺泡上皮细胞坏死和凋亡，但修复过程中细胞死亡的影响尚未确定。我们在原代大鼠肺泡 II 型 (ATII) 细胞划伤模型中检查了循环拉伸 (CS) 期间的上皮修复，发现 CS 改变了增殖和细胞死亡之间的平衡。我们测量了细胞迁移、大小和密度；细胞间隙的形成；细胞数量、增殖和凋亡；细胞骨架组织；和针对划伤的粘着斑，然后进行长达 24 小时的 CS。在静态条件下，伤口在 24 小时内闭合，但修复受到 CS 的抑制。伤口刺激细胞运动和增殖、肌动蛋白和纽蛋白重新分布以及伤口边缘的粘着斑形成，而CS阻碍细胞扩散、引发细胞凋亡、刺激细胞骨架重组并减弱粘着斑形成。与静态细胞相比，CS 还导致显着的细胞间间隙形成。我们的结果表明，CS 改变了上皮修复的多种机制，并且细胞死亡和增殖之间发生了不平衡，必须克服这种不平衡才能恢复上皮屏障。
Crosby LM, Luellen C, Zhang Z, Tague LL, Sinclair SE, Waters CM. Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing. Am J Physiol Lung Cell Mol Physiol 301: L536-L546, 2011. First published July 1, 2011; doi: 10.1152/ajplung.00371.2010.-After acute lung injury, repair of the alveolar epithelium occurs on a substrate undergoing cyclic mechanical deformation. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. We examined epithelial repair during cyclic stretch (CS) in a scratch-wound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caused significant intercellular gap formation compared with static cells. Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier.