Yi Sheng, Tang Xin, Yu Jun, Liu Jie, Ding Fei, Gu Xiaosong
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University Nantong, China.
Front Cell Neurosci. 2017 Feb 10;11:22. doi: 10.3389/fncel.2017.00022. eCollection 2017.
Wallerian degeneration occurs immediately following injury to mammal peripheral nerves. To better understand the molecular events occurring during Wallerian degeneration, a rat model of sciatic nerve transection was used to assess differentially expressed genes at 0.5, 1, 6, 12, 24 h, 4 days, 1, 2, 3, and 4 weeks post nerve injury (PNI). Hierarchical clustering, Euclidean distance matrix, and principal component analysis (PCA) collectively suggested three distinct phases within the post-injury period of 4 weeks. Gene ontology (GO) analysis suggested that phase I (0-6 h PNI), phase II (6-24 h PNI), and phase III (4 days to 4 weeks) were associated with acute response to injury, preformation of Wallerian degeneration, and complete execution of Wallerian degeneration, respectively. Critical signaling pathways and transcriptional factor networks responsible for the regulation of Wallerian degeneration were further identified and integrated using Kyoto Enrichment of Genes and Genomes (KEGG) pathway analysis and Ingenuity Pathway Analysis (IPA), respectively. Our results may help to elucidate some molecular mechanisms of gene regulation associated with Wallerian degeneration that occurs after traumatic injury to peripheral nerve axons in mammals.
沃勒变性发生在哺乳动物外周神经损伤后立即出现。为了更好地理解沃勒变性过程中发生的分子事件，使用坐骨神经横断大鼠模型来评估神经损伤后（PNI）0.5、1、6、12、24小时、4天、1、2、3和4周时差异表达的基因。层次聚类、欧几里得距离矩阵和主成分分析（PCA）共同表明在4周的损伤后时期内有三个不同阶段。基因本体（GO）分析表明，第一阶段（PNI后0 - 6小时）、第二阶段（PNI后6 - 24小时）和第三阶段（4天至4周）分别与损伤的急性反应、沃勒变性的预形成和沃勒变性的完全执行相关。分别使用京都基因与基因组百科全书（KEGG）通路分析和 Ingenuity 通路分析（IPA）进一步鉴定和整合了负责调节沃勒变性的关键信号通路和转录因子网络。我们的结果可能有助于阐明与哺乳动物外周神经轴突创伤性损伤后发生的沃勒变性相关的基因调控的一些分子机制。
