中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (11): 2116-2122.doi: 10.4103/1673-5374.282263

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

基质金属蛋白酶7诱导许旺细胞基因变化的测序分析

  

  • 出版日期:2020-11-15 发布日期:2020-08-23
  • 基金资助:

    江苏省高等学校优先学术计划项目

Sequencing analysis of matrix metalloproteinase 7-induced genetic changes in Schwann cells

Pan-Jian Lu, Gang Wang, Xiao-Dong Cai, Ping Zhang, Hong-Kui Wang   

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2020-11-15 Published:2020-08-23
  • Contact: Hong-Kui Wang, MD,wanghongkui@ntu.edu.cn.
  • Supported by:
    This work was supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions of China [PAPD].

摘要:

既往研究显示基质金属蛋白酶7与许旺细胞的迁移和髓鞘再生的活性有关,但目前对过表达的基质金属蛋白酶7导致许旺细胞中的细胞因子表达变化和生物学活性的了解仍然有限。为更好地理解其潜在分子机制,实验从新生大鼠坐骨神经残端分离培养原代许旺细胞,以10 nM人基质金属蛋白酶7干预24h后进行基因检测,在相对宽松的阈值(倍数变化≥1.5,P<0.05)下,(1)发现其中149种基因表达上调,133种基因表达下调;(2)GO分析可见,这些差异表达的基因与细胞过程、单一生物器过程与代谢过程有关;(3)KEGG通路分析进一步显示,与细胞信号传导和代谢相关的基因参与基质金属蛋白酶7诱导的许旺细胞这一过程;(4)创新途径分析(IPA)结果也显示,基质金属蛋白酶7还可调节生物过程、分子功能、细胞组分、疾病与功能、生物合成、物质代谢及细胞运动和轴突导向等过程;(5)这一结果有助于加深对基质金属蛋白酶7诱导的许旺细胞生物学变化潜在机制的了解。动物实验于2019年2月27日经江苏实验动物伦理委员会批准(批准号20190225-004)。

orcid: 0000-0002-8778-4682 (Hong-Kui Wang)

关键词:

基质金属蛋白酶7, 许旺细胞, 周围神经再生, 坐骨神经损伤, RNA测序, 生物信息学分析, 创新途径分析

Abstract: Previous research revealed the positive activity of matrix metalloproteinase 7 (MMP7) on migration and myelin regeneration of Schwa nn cells (SCs). However, understanding of the molecular changes and biological activities induced by increased amounts of MMP7 in SCs remains limited. To better understand the underlying molecular events, primary SCs were isolated from the sciatic nerve stump of new- born rats and cultured with 10 nM human MMP7 for 24 hours. The results of genetic testing were analyzed at a relatively relaxed threshold value (fold change ≥ 1.5 and P-value < 0.05). Upon MMP7 exposure, 149 genes were found to be upregulated in SCs, whereas 133 genes were downregulated. Gene Ontology analysis suggested that many differentially expressed molecules were related to cellular processes, sin- gle-organism processes, and metabolic processes. Kyoto Enrichment of Genes and Genomes pathway analysis further indicated the critical involvement of cell signaling and metabolism in MMP7-induced molecular regulation of SCs. Results of Ingenuity Pathway Analysis (IPA) also revealed that MMP7 regulates biological processes, molecular functions, cellular components, diseases and functions, biosynthesis, material metabolism, cell movement, and axon guidance. The outcomes of further analysis will deepen our comprehension of MMP7-in- duced biological changes in SCs. This study was approved by the Laboratory Animal Ethics Committee of Nantong University, China (approval No. 20190225-004) on February 27, 2019.

Key words: bioinformatic analysis, ingenuity pathway analysis, matrix metalloproteinase 7, peripheral nerve regeneration, RNA sequencing, Schwann cells, sciatic nerve injury