Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat
Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat
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DOI：
10.1007/s12264-013-1340-0
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发表时间：
2013-06-01
影响因子：
5.6
通讯作者：
Gu, Xiaosong
中科院分区：
文献类型：
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作者：
Yao, Dengbing;Li, Meiyuan;Gu, Xiaosong
沃勒氏变性（WD）仍然是一个重要的研究课题。在WD过程中，许多基因存在差异表达，但导致这些差异的确切机制尚不完全清楚。在本研究中，我们采用微阵列技术分析大鼠坐骨神经损伤后0、1、4、7、14、21和28天远端神经残端表达的变化。数据显示有6076个差异表达基因，23种表达类型，特别富集与神经发育和轴突发生、细胞因子生物合成、细胞分化、细胞因子/趋化因子产生、神经元分化、细胞分裂、磷酸化和轴突再生相关的基因。京都基因与基因组百科通路分析主要涉及MAPK信号通路、Jak-STAT信号通路、细胞周期、细胞因子-细胞因子受体相互作用、p53信号通路和Wnt信号通路。关键因子为NGF、MAG、CNTF、CTNNA2、p53、JAK2、PLCB1、STAT3、BDNF、PRKC、collagen II、FGF、THBS4、TNC和c-Src，并通过实时定量PCR、Western blot和免疫组化进一步验证。我们的发现有助于更好地理解WD中差异表达基因的功能分析，并可能揭示神经变性和再生的分子机制。
Wallerian degeneration (WD) remains an important research topic. Many genes are differentially expressed during the process of WD, but the precise mechanisms responsible for these differentiations are not completely understood. In this study, we used microarrays to analyze the expression changes of the distal nerve stump at 0, 1, 4, 7, 14, 21 and 28 days after sciatic nerve injury in rats. The data revealed 6 076 differentially-expressed genes, with 23 types of expression, specifically enriched in genes associated with nerve development and axonogenesis, cytokine biosynthesis, cell differentiation, cytokine/chemokine production, neuron differentiation, cytokinesis, phosphorylation and axon regeneration. Kyoto Encyclopedia of Genes and Genomes pathway analysis gave findings related mainly to the MAPK signaling pathway, the Jak-STAT signaling pathway, the cell cycle, cytokine-cytokine receptor interaction, the p53 signaling pathway and the Wnt signaling pathway. Some key factors were NGF, MAG, CNTF, CTNNA2, p53, JAK2, PLCB1, STAT3, BDNF, PRKC, collagen II, FGF, THBS4, TNC and c-Src, which were further validated by real-time quantitative PCR, Western blot, and immunohistochemistry. Our findings contribute to a better understanding of the functional analysis of differentially-expressed genes in WD and may shed light on the molecular mechanisms of nerve degeneration and regeneration.