Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction
Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction
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DOI：
10.1152/ajpcell.00207.2004
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发表时间：
2005-01-01
影响因子：
5.5
通讯作者：
Esser, KA
中科院分区：
文献类型：
--
作者：
Hornberger, TA;Armstrong, DD;Esser, KA
一些证据表明，肌肉细胞可以区分特定的机械刺激。为了验证这一概念，我们对C2C12肌管进行了单轴或多轴循环拉伸。两种拉伸均诱导细胞外信号调节激酶（ERK）和蛋白激酶B （PKB/Akt）磷酸化增加，但仅多轴拉伸诱导核糖体S6激酶（p70(S6k)）磷酸化。进一步的结果表明，多轴拉伸特异性的信号事件（p70（S6k）磷酸化）是由通过弹性培养膜传递的力引起的，而不是由于更大的表面积变形或大拉伸应变的局部区域。用多轴拉伸肌管调节的培养基进行的实验表明，旁分泌因子的释放不足以诱导p70信号传导（S6k）。此外，用氯化钆（III） （500 muM）、染料木素（250 muM）、PD-98059 （250 muM）、双吲哚马来酰亚胺I （20 muM）或LY-294002 （100 muM）孵育也不会阻断p70（S6k）的多轴拉伸诱导信号。然而，用细胞松弛素D破坏肌动蛋白细胞骨架确实阻断了p70（S6k）的多轴信号传导，而对PKB/Akt的信号传导没有影响。这些结果表明，特定类型的机械拉伸激活了不同的信号通路，我们认为这是通过直接的机械感觉-机械转导机制发生的，而不是通过先前定义的生长因子/受体结合途径。
Several lines of evidence suggest that muscle cells can distinguish between specific mechanical stimuli. To test this concept, we subjected C2C12 myotubes to cyclic uniaxial or multiaxial stretch. Both types of stretch induced an increase in extracellular signal-regulated kinase (ERK) and protein kinase B (PKB/Akt) phosphorylation, but only multiaxial stretch induced ribosomal S6 kinase (p70(S6k)) phosphorylation. Further results demonstrated that the signaling events specific to multiaxial stretch (p70(S6k) phosphorylation) were elicited by forces delivered through the elastic culture membrane and were not due to greater surface area deformations or localized regions of large tensile strain. Experiments performed using medium that was conditioned by multiaxial stretched myotubes indicated that a release of paracrine factors was not sufficient for the induction of signaling to p70(S6k). Furthermore, incubation with gadolinium(III) chloride (500 muM), genistein (250 muM), PD-98059 (250 muM), bisindolylmaleimide I (20 muM), or LY-294002 (100 muM) did not block the multiaxial stretch-induced signaling to p70(S6k). However, disrupting the actin cytoskeleton with cytochalasin D did block the multiaxial signaling to p70(S6k), with no effect on signaling to PKB/Akt. These results demonstrate that specific types of mechanical stretch activate distinct signaling pathways, and we propose that this occurs through direct mechanosensory-mechanotransduction mechanisms and not through previously defined growth factor/receptor binding pathways.