PI3K-GSK3 signalling regulates mammalian axon regeneration by inducing the expression of Smad1.

PI3K-GSK3 signalling regulates mammalian axon regeneration by inducing the expression of Smad1.
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DOI:
10.1038/ncomms3690
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发表时间:
2013
影响因子:
16.6
通讯作者:
Zhou, Feng-Quan
Zhou, Feng-Quan
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Saijilafu;Hur, Eun-Mi;Liu, Chang-Mei;Jiao, Zhongxian;Xu, Wen-Lin;Zhou, Feng-Quan

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与中枢神经系统中的神经元相反,哺乳动物周围神经系统中的成熟神经元可以在损伤后部分地通过增强内在生长能力来再生轴突。然而,增强生长潜力和诱导自发轴突再生的信号通路仍然知之甚少。在这里,我们发现,磷脂酰肌醇3-激酶(PI 3 K)信号被激活,在响应外周神经切断和PI 3 K通路是必需的感觉轴突再生。此外,我们表明,糖原合成酶激酶3(GSK 3),而不是哺乳动物雷帕霉素的目标,介导的PI 3 K依赖性增强周围神经系统的生长潜力。此外,我们表明,PI 3 K-GSK 3信号通过诱导转录因子Smad 1来传递,并且成年小鼠中Smad 1的急性耗竭阻止了体内轴突再生。总之,这些结果表明PI 3 K-GSK 3-Smad 1信号传导作为促进哺乳动物神经系统中感觉轴突再生的中枢模块。
In contrast to neurons in the central nervous system, mature neurons in the mammalian peripheral nervous system can regenerate axons after injury, in part, by enhancing intrinsic growth competence. However, the signalling pathways that enhance the growth potential and induce spontaneous axon regeneration remain poorly understood. Here we reveal that phosphatidylinositol 3-kinase (PI3K) signalling is activated in response to peripheral axotomy and that PI3K pathway is required for sensory axon regeneration. Moreover, we show that glycogen synthase kinase 3 (GSK3), rather than mammalian target of rapamycin, mediates PI3K-dependent augmentation of the growth potential in the peripheral nervous system. Furthermore, we show that PI3K-GSK3 signal is conveyed by the induction of a transcription factor Smad1 and that acute depletion of Smad1 in adult mice prevents axon regeneration in vivo. Together, these results suggest PI3K-GSK3-Smad1 signalling as a central module for promoting sensory axon regeneration in the mammalian nervous system.
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