Changes in Fibroblast Mechanostat Set Point and Mechanosensitivity: An Adaptive Response to Mechanical Stress in Floppy Eyelid Syndrome
Changes in Fibroblast Mechanostat Set Point and Mechanosensitivity: An Adaptive Response to Mechanical Stress in Floppy Eyelid Syndrome
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DOI：
10.1167/iovs.09-4724
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发表时间：
2010-08-01
影响因子：
4.4
通讯作者：
Bailly, Maryse
中科院分区：
文献类型：
--
作者：
Ezra, Daniel G.;Ellis, James S.;Bailly, Maryse
目的.眼睑松弛综合征（FES）是一种影响上眼睑的获得性超弹性疾病。睑板变得超弹性，固有刚度丧失。结果，眼睑受到周期性机械应力。这种情况被用来作为一个模型，以研究在慢性循环机械应力的背景下，动态成纤维细胞收缩力的变化。在自由漂浮的三维胶原基质模型中研究收缩效率。使用张力培养力监测仪（t-CFM）探讨了细胞内力测量和对凝胶张力变化的反应。利用基因组水平的微阵列平台和RT-PCR技术研究了收缩表型差异的细胞系之间的基因表达差异。与对照组相比，FES睑板成纤维细胞（TF）显示出增加的收缩效率，t-CFM测量证实了在平台水平具有更高的内在细胞力。循环拉伸/松弛实验确定，在FES中的TF保持功能性张力稳态响应，但具有改变的灵敏度，在更高的mechanostat设定点附近操作。基因表达阵列和RT-PCR分析证实V-CAM 1和PPP 1 R3 C在FES TF中上调。这些变化可能代表了一种适应性反应，允许在FES中经历的高水平组织应力下维持张力稳态。基因表达研究指出V-CAM 1和PPP 1 R3 C在介导TF机械敏感性动态范围变化中的作用。这项工作确定FES作为一个有用的模型，用于研究适应性生理反应的机械应力。（Invest Ophthalmol维斯科学。2010; 51：3853-3863）DOI：10.1167/iovs.09-4724
PURPOSE. Floppy eyelid syndrome (FES) is an acquired hyperelasticity disorder affecting the upper eyelid. The tarsal plate becomes hyperelastic with a loss of intrinsic rigidity. As a result, the eyelid is subjected to cyclic mechanical stress. This condition was used as a model to investigate changes in dynamic fibroblast contractility in the context of chronic cyclic mechanical stress.METHODS. Contractile efficiency was investigated in a free-floating, three-dimensional collagen matrix model. Intrinsic cellular force measurements and responses to changes in gel tension were explored using a tensioning culture force monitor (t-CFM). Gene expression differences between cell lines exhibiting differences in contractile phenotype were explored with a genome level microarray platform and RT-PCR.RESULTS. FES tarsal plate fibroblasts (TFs) showed an increased contractile efficiency compared with the control, and t-CFM measurements confirmed a higher intrinsic cellular force at plateau levels. Cyclic stretch/relaxation experiments determined that TFs in FES maintained a functional tensional homeostasis response but with an altered sensitivity, operating around a higher mechanostat set point. Gene expression array and RT-PCR analysis identified V-CAM1 and PPP1R3C as being upregulated in FES TFs.CONCLUSIONS. These changes may represent an adaptive response that allows tensional homeostasis to be maintained at the high levels of tissue stress experienced in FES. Gene expression studies point to a role for V-CAM1 and PPP1R3C in mediating changes in the dynamic range of mechanosensitivity of TFs. This work identifies FES as a useful model for the study of adaptive physiological responses to mechanical stress. (Invest Ophthalmol Vis Sci. 2010; 51: 3853-3863) DOI: 10.1167/iovs.09-4724