中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (6): 995-1002.doi: 10.4103/1673-5374.208596

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

周围神经瓦勒变性中的关键信号通路

  

  • 收稿日期:2017-05-17 出版日期:2017-06-15 发布日期:2017-06-15
  • 基金资助:

     

    中国国家自然科学基金项目(81501058; 江苏省自然科学基金项目(BK20150409; 江苏省高等院校自然科学基金项目(15KJB180013, 15KJB310014; 江苏省高等院校重点学科建设项目

Critical signaling pathways during Wallerian degeneration of peripheral nerve

Qiong Cheng, Ya-xian Wang, Jun Yu, Sheng Yi   

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Received:2017-05-17 Online:2017-06-15 Published:2017-06-15
  • Contact: Sheng Yi, Ph.D., syi@ntu.edu.cn.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81501058; the Natural Science Foundation of Jiangsu Province of China, No. BK20150409; the Natural Science Foundation of Jiangsu Higher Education Institutions of China, No. 15KJB180013, 15KJB310014; and a grant from the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.

摘要:

瓦勒变性是一个重要的生物学过程,在神经损伤后神经远端发生。为了全面研究瓦勒变性的分子机制,实验对大鼠损伤坐骨神经横断后0,0.5,1,6,12,24h,4d,1,2,3,4周损伤远侧端差异表达的基因进行了系统的微阵列分析,探索周围神经损伤后不同时间点神经远端的KEGG通路的变化。生物信息学结果表明,细胞因子与其受体间的相互作用的KEGG通路在损伤后早期发生明显变化。随着损伤后时间的延长,发生变化的KEGG通路数量先升后降。我们对细胞因子与其受体间的相互作用、神经活性物质与其受体间的相互作用和轴突引导3条通路进行进一步分析。然后以RT-PCR验证上述KEGG通路典型基因的变化。结果提示发现细胞因子与其受体间的相互作用、神经活性物质与其受体间的相互作用以及轴突引导这3条信号通路在瓦勒变性过程中尤为重要,这为瓦勒变性分子机制的研究提供了良好基础。

ORCID:0000-0003-1316-3370(Sheng Yi)

关键词: 神经再生, 瓦勒变性, 坐骨神经损伤, 周围神经再生, 基因芯片, 生物信息学分析, KEGG, 信号通路, 细胞因子与其受体间的相互作用, 神经活性物质与其受体间的相互作用, 轴突引导

Abstract:

Wallerian degeneration is a critical biological process that occurs in distal nerve stumps after nerve injury. To systematically investigate molecular changes underlying Wallerian degeneration, we used a rat sciatic nerve transection model to examine microarray analysis outcomes and investigate significantly involved Kyoto Enrichment of Genes and Genomes (KEGG) pathways in injured distal nerve stumps at 0, 0.5, 1, 6, 12, and 24 hours, 4 days, 1, 2, 3, and 4 weeks after peripheral nerve injury. Bioinformatic analysis showed that only one KEGG pathway (cytokine-cytokine receptor interaction) was significantly enriched at an early time point (1 hour post-sciatic nerve transection). At later time points, the number of enriched KEGG pathways initially increased and then decreased. Three KEGG pathways were studied in further detail: cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and axon guidance. Moreover, temporal expression patterns of representative differentially expressed genes in these KEGG pathways were validated by real time-polymerase chain reaction. Taken together, the above three signaling pathways are important after sciatic nerve injury, and may increase our understanding of the molecular mechanisms underlying Wallerian degeneration.

Key words: nerve regeneration, Wallerian degeneration, sciatic nerve transection, peripheral nerve regeneration, microarray, bioinformatic analysis, Kyoto Enrichment of Genes and Genomes, signaling pathway, cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, axon guidance, neural regeneration