Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells
Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells
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DOI：
10.1016/j.yexcr.2012.05.021
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发表时间：
2012-08-15
影响因子：
3.7
通讯作者：
Ushida, Takashi
中科院分区：
文献类型：
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作者：
Horiuchi, Rie;Akimoto, Takayuki;Ushida, Takashi
据报道，机械应变会影响许多细胞类型的增殖/分化；然而，机械转导对胚胎干细胞自我更新和多能性的影响仍然未知。为了研究机械应变对小鼠 ES 细胞命运的影响，我们检测了 Nanog 的表达，Nanog 是单轴循环机械应变期间自我更新和多能性以及 Nanog 相关细胞内信号传导的重要调节因子。将小鼠 ES 细胞系 CCE 铺板到弹性膜上，并在 0.17 Hz 下施加 10% 应变。 Nanog 的表达在 ES 细胞分化过程中随着白血病抑制因子 (LIF) 的退出而降低；然而，两天的循环机械应变减弱了 Nanog 表达的减少。另一方面，循环机械应变促进了 PI3K-Akt 信号传导，据报道该信号传导是 Nanog 转录的上游。 PI3K 抑制剂渥曼青霉素可减弱循环机械应变诱导的 Akt 磷酸化作用。此外，肌动蛋白聚合抑制剂细胞松弛素 D 也抑制机械应变诱导的磷酸-Akt 增加。这些发现表明机械力通过肌动蛋白细胞骨架-PI3K-Akt 信号传导在调节 ES 细胞中 Nanog 表达中发挥作用。 (C) 2012 Elsevier Inc. 保留所有权利。
Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling. (C) 2012 Elsevier Inc. All rights reserved.