Mechanical stimulation of cyclic tensile strain induces reduction of pluripotent related gene expressions via activation of Rho/ROCK and subsequent decreasing of AKT phosphorylation in human induced pluripotent stem cells.
Mechanical stimulation of cyclic tensile strain induces reduction of pluripotent related gene expressions via activation of Rho/ROCK and subsequent decreasing of AKT phosphorylation in human induced pluripotent stem cells.
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DOI：
10.1016/j.bbrc.2011.12.052
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发表时间：
2012-01
影响因子：
3.1
通讯作者：
Takeshi Teramura;Toshiyuki Takehara;Yuta Onodera;Koichi Nakagawa;C. Hamanishi;Kanji Fukuda
中科院分区：
文献类型：
--
作者：
Takeshi Teramura;Toshiyuki Takehara;Yuta Onodera;Koichi Nakagawa;C. Hamanishi;Kanji Fukuda
机械刺激已被证明可以调节干细胞的增殖和分化。然而，机械应力对干度的影响或相关的分子机制尚未得到很好的确定。多能干细胞如胚胎干（ES）细胞和诱导性多能干（iPS）细胞是用于细胞移植治疗和哺乳动物发育研究的良好材料，因为它们可以无限地自我更新并分化成各种细胞谱系。在这里，我们证明了对人类iPS细胞的机械刺激改变了肌动蛋白纤维的排列和多能相关基因Nanog，POU 5 f1和Sox 2的表达。在机械刺激的iPS细胞中，小GTdR Rho被激活，有趣的是，AKT磷酸化降低。抑制Rho相关激酶ROCK可恢复AKT磷酸化和基因表达。这些结果清楚地表明Rho/ROCK是多能干细胞中机械应力的有效初级效应子，并且其作为上游调节剂参与多能性相关的信号级联。
Mechanical stimulation has been shown to regulate the proliferation and differentiation of stem cells. However, the effects of the mechanical stress on the stemness or related molecular mechanisms have not been well determined. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are used as good materials for cell transplantation therapy and research of mammalian development, since they can self-renew infinitely and differentiate into various cell lineages. Here we demonstrated that the mechanical stimulation to human iPS cells altered alignment of actin fibers and expressions of the pluripotent related genes Nanog, POU5f1 and Sox2. In the mechanically stimulated iPS cells, small GTPase Rho was activated and interestingly, AKT phosphorylation was decreased. Inhibition of Rho-associated kinase ROCK recovered the AKT phosphorylation and the gene expressions. These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator.