Mechanical role of nesprin-1-mediated nucleus-actin filament binding in cyclic stretch-induced fibroblast elongation
Mechanical role of nesprin-1-mediated nucleus-actin filament binding in cyclic stretch-induced fibroblast elongation
复制标题
Nesprin-1介导的核肌动蛋白丝结合在循环拉伸诱导的成纤维细胞伸长中的机械作用
DOI：
10.1007/s12195-017-0487-6
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发表时间：
2017
影响因子：
2.8
通讯作者：
N. Kataoka
中科院分区：
文献类型：
--
作者：
N. Sakamoto;M. Ogawa;K. Sadamoto;M. Takeuchi;N. Kataoka
将细胞核与细胞骨架相连的细胞内机械连接被认为是核骨架和细胞骨架（LINC）复合物的连接器。先前的研究报告称，Nesprin-1（LINC复合物的一种成分，直接与肌动蛋白丝结合）的敲除可抑制细胞对机械刺激的形态反应。然而，nesprin-1 敲低与细胞形态变化之间的关系仍不清楚。在这项研究中，我们研究了核-肌动蛋白丝结合在暴露于循环拉伸的成纤维细胞形态变化中的机械作用。暴露于 10% 循环拉伸 6 小时后，与未转染的细胞相比，转染 Nesprin-1 特异性小干扰 RNA 的成纤维细胞显示出更少的拉长形状。为了进一步研究细胞核和细胞核结合肌动蛋白丝的机械作用，我们对用曲古抑菌素 A (TSA) 处理的成纤维细胞进行循环拉伸，这降低了细胞核的硬度，从而降低了细胞核结合肌动蛋白丝的张力。研究发现，在静态和循环拉伸条件下，TSA 处理比未处理的细胞诱导出更圆形的细胞形状。这些结果表明，核结合肌动蛋白丝的张力在循环拉伸下细长成纤维细胞的形成中起着重要作用，并且nesprin-1敲除导致核相关肌动蛋白丝张力降低。
The intracellular mechanical link tethering the nucleus to the cytoskeleton has been suggested to be the linker of the nucleoskeleton and cytoskeleton (LINC) complex. Previous studies have reported that knockdown of nesprin-1, a component of the LINC complex that directly binds to actin filaments, suppresses cellular morphological response to mechanical stimuli. The relation between nesprin-1 knockdown and cellular morphological changes, however, remains unclear. In this study, we examined the mechanical role of nucleus–actin filament binding in morphological changes of fibroblasts exposed to cyclic stretching. After exposure to 10% cyclic stretching for 6 h, fibroblasts transfected with nesprin-1-specific small interfering RNA showed fewer elongated shapes compared with non-transfected cells. To further examine the mechanical role of the nucleus and nucleus-bound actin filaments, we applied cyclic stretching to fibroblasts treated with Trichostatin A (TSA), which decreases nuclear stiffness and thereby reduces nucleus-binding actin filament tension. TSA-treatment was found to induce more rounded cellular shapes than those of non-treated cells under both static and cyclic stretching conditions. These results suggest that the tension of nucleus-bound actin filaments plays an important role in the formation of elongated fibroblasts under cyclic stretching and that nesprin-1 knockdown causes a decrease of tension in nucleus-associated actin filaments.