中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (9): 1622-1627.doi: 10.4103/1673-5374.237183

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

周围神经损伤后背根神经节细胞死亡的转录因子网络

  

  • 收稿日期:2018-06-09 出版日期:2018-09-15 发布日期:2018-09-15
  • 基金资助:

    国家自然科学基金(31500823);江苏省自然科学基金(31500823);江苏省高校自然科学基金(16KJB180024

Transcription factor networks involved in cell death in the dorsal root ganglia following peripheral nerve injury

Jing Qin1, 2, Jian-Cheng Wu1, Qi-Hui Wang1, Song-Lin Zhou1, Su-Su Mao1, Chun Yao1   

  1. 1 Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
    2 Department of Pathological Anatomy, Nantong University, Nantong, Jiangsu Province, China
  • Received:2018-06-09 Online:2018-09-15 Published:2018-09-15
  • Contact: Chun Yao, Ph.D.,yaochun@ntu.edu.cn
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 31500823; the Natural Science Foundation of Jiangsu Province of China, No. BK20150403; the Natural Science Fund for Colleges and Universities in Jiangsu Province of China, No.16KJB180024.

摘要:

神经损伤后其神经元内在的再生能力和适宜的微环境而具有再生潜能,这一过程涉及大量基因的表达变化。作为一种调节基因转录的蛋白,转录因子在神经再生中发挥了重要作用。课题组以往研究已经通过RNA测序获取了大鼠坐骨神经损伤后不同时间点(0,3 h,9 h,1 d,4 d 和7 d)背根神经节神经元中异常表达的基因谱。本组实验进一步取大鼠坐骨神经损伤后不同时间点(0,3 h,9 h,1 d,4 d 和7 d)背根节神经元观察转录因子的差异表达,并且通过IPA分析系统确认这些转录因子富集的分子和细胞功能。基因和功能网络分析结果显示,坐骨神经损伤后不同时间点细胞死亡过程中相关转录因子呈动态表达变化。此外,实验还构建了细胞死亡中差异表达的转录因子的调控网络,发现了关键转录因子STAT1,JUN,MYC 和 IRF7,并通过实时PCR验证了STAT1和IRF7的基因表达变化。实验通过对坐骨神经损伤后背根神经节组织转录因子进行分析,提供了参与细胞死亡的转录因子基因的调控网络。

orcid:0000-0002-3706-955X(Chun Yao)

 

关键词: 细胞死亡, 转录因子, 背根神经节细胞, 外周神经损伤, 坐骨神经, IPA分析, Cytoscape, 生物信息学分析, STAT1, IRF7

Abstract:

The peripheral nervous system has the potential to regenerate after nerve injury owing to the intrinsic regrowth ability of neurons and the permissive microenvironment. The regenerative process involves numerous gene expression changes, in which transcription factors play a critical role. Previously, we profiled dysregulated genes in dorsal root ganglion neurons at different time points (0, 3 and 9 hours, and 1, 4 and 7 days) after sciatic nerve injury in rats by RNA sequencing. In the present study, we investigated differentially expressed transcription factors following nerve injury, and we identified enriched molecular and cellular functions of these transcription factors by Ingenuity Pathway Analysis. This analysis revealed the dynamic changes in the expression of transcription factors involved in cell death at different time points following sciatic nerve injury. In addition, we constructed regulatory networks of the differentially expressed transcription factors in cell death and identified some key transcription factors (such as STAT1, JUN, MYC and IRF7). We confirmed the changes in expression of some key transcription factors (STAT1 and IRF7) by quantitative reverse transcription-polymerase chain reaction. Collectively, our analyses provide a global overview of transcription factor changes in dorsal root ganglia after sciatic nerve injury and offer insight into the regulatory transcription factor networks involved in cell death.

Key words: nerve regeneration, cell death, transcription factors, dorsal root ganglia neurons, peripheral nerve injury, sciatic nerve, ingenuity pathway analysis, Cytoscape, bioinformatics analysis, STAT1, IRF7, neural regeneration