中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (7): 1165-1171.doi: 10.4103/1673-5374.187059

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

坐骨神经夹闭伤后个时间点均有基质金属蛋白酶相关差异基因的表达变化

  

  • 出版日期:2016-07-30 发布日期:2016-07-30
  • 基金资助:
    江苏省自然科学基金的资助（bk20150409）；江苏省高校自然科学基金（15kjb180013）；南通大学科学研究基金（14r29）；南通省自然科学基金（ms12015043）；和江苏高校优势学科程序开发项目（PAPD）

Differential temporal expression of matrix metalloproteinases following sciatic nerve crush

Jing Qin#, Guang-bin Zha#, Jun Yu, Hong-hong Zhang, Sheng Yi*   

  1. Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2016-07-30 Published:2016-07-30
  • Contact: Sheng Yi, Ph.D., syi@ntu.edu.cn.
  • Supported by:
    This study was supported by the Natural Science Foundation of Jiangsu Province of China, No. BK20150409; the Natural Science Foundation of Jiangsu Higher Education Institutions of China, No. 15KJB180013; the Scientific Research Foundation of Nantong University in China, No. 14R29; the Natural Science Foundation of Nantong City in China, No. MS12015043; the Priority Academic Program Development of Jiangsu Higher Education Institutions in China.

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摘要：

课题组前期研究采用了转录组测序的方法检测，发现基质金属蛋白酶7，12在大鼠坐骨神经夹闭伤后表达明显上调，这些基因可能参与了周围神经损伤的修复过程。为此，我们在本文中进一步探讨坐骨神经夹闭伤后不同时间点的各种基质金属蛋白酶基因及其相关信号通路调控因子的表达情况。转录组测序结果表明，大鼠坐骨神经夹闭伤后4，7 d，差异表达基因数增多，但在夹闭伤后14 d差异表达基因数显著下降。在这些差异表达基因中，上调最明显的基因上调大于214倍，而下调最明显的基因下调大于2-10倍。基因测序结果显示，大鼠坐骨神经夹闭伤后1，4，7，14 d，“基质金属蛋白酶的抑制”信号通路中多种基质金属蛋白酶基因表达均上调，同时其抑制剂基因表达下调。通过实时定量PCR检测对这些差异表达基因中的部分上调和下调关键基因的表达量进行了验证，得到了与转录组测序相一致的结果。说明坐骨神经夹闭伤后各时间点均可出现诸多基质金属蛋白酶相关差异基因的表达，可能在周围神经再生过程中起重要作用。

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

关键词: 神经再生, 周围神经损伤, 坐骨神经夹闭伤, 转录组测序, 生物信息学分析, 途径, 细胞外基质, 基质金属蛋白酶, 基质金属蛋白酶抑制剂, 整合素, 修复, 再生

Abstract: We previously performed transcriptome sequencing and found that genes for matrix metalloproteinases (MMPs), such as MMP7 and 12, seem to be highly upregulated following peripheral nerve injury, and may be involved in nerve repair. In the present study, we systematically determined the expression levels of MMPs and their regulators at 1, 4, 7 and 14 days after sciatic nerve crush injury. The number of differentially expressed genes was elevated at 4 and 7 days after injury, but decreased at 14 days after injury. Among the differentially expressed genes, those most up-regulated showed fold changes of more than 214, while those most down-regulated exhibited fold changes of more than 2?10. Gene sequencing showed that, at all time points after injury, a variety of MMP genes in the “Inhibition of MMPs” pathway were up-regulated, and their inhibitor genes were down-regulated. Expression of key up- and down-regulated genes was verified by quantitative real-time polymerase chain reaction analysis and found to be consistent with transcriptome sequencing. These results suggest that MMP-related genes are strongly involved in the process of peripheral nerve regeneration.

Key words: nerve regeneration, peripheral nerve injury, sciatic nerve crush, transcriptome sequencing, bioinformatic analysis, canonical pathway, extracellular matrix, matrix metalloproteinase, tissue inhibitors of metalloproteinase, disintegrin, repair, neural regeneration