Transcriptomic Landscapes of Immune Response and Axonal Regeneration by Integrative Analysis of Molecular Pathways and Interactive Networks Post-sciatic Nerve Transection.

Transcriptomic Landscapes of Immune Response and Axonal Regeneration by Integrative Analysis of Molecular Pathways and Interactive Networks Post-sciatic Nerve Transection.
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通过坐骨神经横断后分子途径和交互网络的综合分析免疫反应和轴突再生的转录组景观

DOI:
10.3389/fnins.2018.00457
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发表时间:
2018
影响因子:
4.3
通讯作者:
Cui S
Cui S
中科院分区:
医学2区
文献类型:
--
作者:
Guo Q;Zhu H;Wang H;Zhang P;Wang S;Sun Z;Li S;Xue C;Gu X;Cui S

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免疫反应与轴突再生之间的相互作用是近年来周围神经系统研究的热点。以前,近端神经节段中的整体mRNA表达变化被描绘,并且仅仅关注关键生物过程的差异变化。为了进一步揭示周围神经再生的分子机制,本文重点研究了坐骨神经切断后免疫反应和轴突再生之间的相互作用,这些相互作用与特定的分子通路和相互作用网络有关。为了阐明坐骨神经切断后轴突再生和免疫反应的具体分子通路,并阐明免疫反应和轴突再生之间的分子相互作用,我们进行了包括基因表达谱分析和多水平生物信息学分析在内的综合方法,并进一步进行了实验验证。Alcam、Nrp 1、Nrp 2、Rac 1、Creb 1和Runx 3首次被认为是大鼠坐骨神经切断模型中蛋白质相互作用(PPI)网络的关键或枢纽基因,与免疫反应和轴突再生高度相关。我们的工作为阐明周围神经再生的分子机制提供了新的途径,为揭示神经损伤诱导微环境变化的分子过程,发现轴突再生的新治疗靶点提供了宝贵的资源。
Potential interaction between immune response and axonal regeneration has recently attracted much attention in peripheral nervous system (PNS). Previously, global mRNA expression changes in proximal nerve segments were profiled and merely focused on the differentially change of the key biological processes. To further uncover molecular mechanisms of peripheral nerve regeneration, here we focused on the interaction between immune response and axonal regeneration that associated with specific molecular pathways and interactive networks following sciatic nerve transection. To offer an outline of the specific molecular pathways elaborating axonal regeneration and immune response, and to figure out the molecular interaction between immune response and axonal regeneration post-sciatic nerve transection, we carried out comprehensive approaches, including gene expression profiling plus multi-level bioinformatics analysis and then further experimental validation. Alcam, Nrp1, Nrp2, Rac1, Creb1, and Runx3 were firstly considered as the key or hub genes of the protein-protein interaction (PPI) network in rat models of sciatic nerve transection, which are highly correlated with immune response and axonal regeneration. Our work provide a new way to figure out molecular mechanism of peripheral nerve regeneration and valuable resources to figure out the molecular courses which outline neural injury-induced micro-environmental variation to discover novel therapeutic targets for axonal regeneration.
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