Activation of the transcription factor NF-κB in Schwann cells is required for peripheral myelin formation
Activation of the transcription factor NF-κB in Schwann cells is required for peripheral myelin formation
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DOI：
10.1038/nn995
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发表时间：
2003-02-01
影响因子：
25
通讯作者：
Carter, BD
中科院分区：
文献类型：
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作者：
Nickols, JC;Valentine, W;Carter, BD
外周髓磷脂的形成是由轴突信号启动的，轴突信号触发相关雪旺细胞的分化程序。在这里，我们定义了一种重要的分化信号：转录因子 NF-kappaB 的激活。在大鼠坐骨神经中，髓鞘形成前雪旺细胞中的 NF-κB 高度上调，然后其表达逐渐下降，直至在成人中几乎消失。同样，在雪旺细胞和感觉神经元的共培养中，NF-kappaB 激活与髓鞘形成平行，阻断其活性或使用缺乏 NF-kappaB 亚基 p65 的小鼠细胞可显着减弱髓鞘形成。抑制 NF-kappaB 还可以阻止 Oct-6 的激活，Oct-6 是一种由轴突接触诱导的转录因子，也是正常髓磷脂形成所必需的。这些结果表明，NF-κB 的激活是轴突相关雪旺细胞进展为髓鞘化表型的重要信号。
Peripheral myelin formation is initiated by axonal cues that trigger a differentiation program in associated Schwann cells. Here, we define one essential differentiation signal: activation of the transcription factor NF-kappaB. In rat sciatic nerves, NF-kappaB was highly upregulated in pre-myelinating Schwann cells, and then its expression progressively declined until it was nearly absent in adults. Similarly, in co-cultures of Schwann cells and sensory neurons, NF-kappaB activation paralleled myelination, and blocking its activity or using cells from mice lacking the NF-kappaB subunit p65 markedly attenuated myelination. Inhibiting NF-kappaB also prevented activation of Oct-6, a transcription factor induced by axonal contact and required for proper myelin formation. These results show that the activation of NF-kappaB is an essential signal for the progression of axon-associated Schwann cells into a myelinating phenotype.