Role of RhoA/ROCK-dependent actin contractility in the induction of tenascin-C by cyclic tensile strain
Role of RhoA/ROCK-dependent actin contractility in the induction of tenascin-C by cyclic tensile strain
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DOI：
10.1016/j.yexcr.2005.12.025
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发表时间：
2006-05-01
影响因子：
3.7
通讯作者：
Chiquet, M
中科院分区：
文献类型：
--
作者：
Sarasa-Renedo, A;Tunç-Civelek, V;Chiquet, M
在鸡胚成纤维细胞中，细胞外基质蛋白Tenascin-C的mRNA在循环应变(10%，0.3 Hz，6h)下诱导2倍。这种反应通过抑制Rho依赖的激酶(ROCK)而减弱。RhoA/ROCK信号通路主要参与肌动蛋白的动力学过程。在这里，我们证明了它在调节Tenascin-C表达中的关键作用。循环应变刺激RhoA活化，诱导成纤维细胞收缩。RhoA的化学激活剂协同增强了循环应变对细胞收缩的影响。有趣的是，Tenascin-C的mRNA水平与RhoA/ROCK介导的肌动蛋白收缩程度完全匹配。首先，凝血酶、溶血磷脂酸或秋水仙碱激活RhoA可诱导Tenascin-C mRNA的表达，其程度与菌株相似。其次，RhoA激活剂与循环应变联合可引起Tenascin-C mRNA的超诱导(4-5倍)，而这种超诱导又被岩石抑制所抑制。第三，用Latrunculin A破坏肌动蛋白细胞骨架，取消了化学RhoA激活剂与循环应变结合对tenascin-C mRNA的诱导。最后，我们发现肌球蛋白11的活性是循环应变诱导Tenascin-C所必需的。我们得出结论，RhoA/ROCK控制的肌动蛋白收缩能力在成纤维细胞中具有机械感觉功能，与tenascin-C基因的表达直接相关。以前的RhoA/ROCK激活，无论是通过化学信号还是机械信号，都可能使成纤维细胞对外部张应力更加敏感，例如在伤口愈合期间。(C)2005 Elsevier Inc.保留所有权利。
In chick embryo fibroblasts, the mRNA for extracellular matrix protein tenascin-C is induced 2-fold by cyclic strain (10%, 0.3 Hz, 6 h). This response is attenuated by inhibiting Rho-dependent kinase (ROCK). The RhoA/ROCK signaling pathway is primarily involved in actin dynamics. Here, we demonstrate its crucial importance in regulating tenascin-C expression. Cyclic strain stimulated RhoA activation and induced fibroblast contraction. Chemical activators of RhoA synergistically enhanced the effects of cyclic strain on cell contractility. Interestingly, tenascin-C mRNA levels perfectly matched the extent of RhoA/ROCK-mediated actin contraction. First, RhoA activation by thrombin, lysophosphatidic acid, or colchicine induced tenascin-C mRNA to a similar extent as strain. Second, RhoA activating drugs in combination with cyclic strain caused a super-induction (4- to 5-fold) of tenascin-C mRNA, which was again suppressed by ROCK inhibition. Third, disruption of the actin cytoskeleton with latrunculin A abolished induction of tenascin-C mRNA by chemical RhoA activators in combination with cyclic strain. Lastly, we found that myosin 11 activity is required for tenascin-C induction by cyclic strain. We conclude that RhoA/ROCK-controlled actin contractility has a mechanosensory function in fibroblasts that correlates directly with tenascin-C gene expression. Previous RhoA/ROCK activation, either by chemical or mechanical signals, might render fibroblasts more sensitive to external tensile stress, e.g., during wound healing. (c) 2005 Elsevier Inc. All rights reserved.