Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
Neurosci Bull. 2013 Jun;29(3):321-32. doi: 10.1007/s12264-013-1340-0. Epub 2013 May 23.
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.
Wallerian 变性(WD)仍然是一个重要的研究课题。许多基因在 WD 过程中表达差异,但负责这些差异的确切机制尚不完全清楚。在这项研究中,我们使用微阵列分析了大鼠坐骨神经损伤后 0、1、4、7、14、21 和 28 天远端神经残端的表达变化。数据显示有 6076 个差异表达基因,有 23 种表达类型,特异性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全书通路分析的结果主要与 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 信号通路有关。一些关键因子包括 NGF、MAG、CNTF、CTNNA2、p53、JAK2、PLCB1、STAT3、BDNF、PRKC、胶原 II、FGF、THBS4、TNC 和 c-Src,这些因子通过实时定量 PCR、Western blot 和免疫组织化学进一步得到验证。我们的研究结果有助于更好地理解 WD 中差异表达基因的功能分析,并可能为神经变性和再生的分子机制提供启示。