Department of Orthopedics, The 98th Military Hospital, Huzhou, Zhejiang Province, China.
Eur Rev Med Pharmacol Sci. 2013 Nov;17(21):2941-8.
The aim of this study was to investigate the gene expression profile of thoracic propriospinal neurons between post-injury rat and controls.
Microarray dataset GSE20907 was downloaded from GEO database, including 12 Spinal Cord Injury (SCI) rat and 12 controls. Student's t test was employed to identified differentially expressed genes with a fold-change > 1.2. Then, we used DAVID to perform functional enrichment analysis to uncover dysfunctional biological processes and molecular signatures database (MsigDB) to find any potential relationship between SCI gene expression signature and other published gene expression signature. Protein-Protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Functional analysis of the hub protein was performed by BinGO.
The maximum change of gene expression profile was found at 3-days post injury and immune response was found upregulated all tested time points. Interestingly, genes upregulated 2-weeks post injury was found significantly overlapped with genes upregulated in brains from Alzheimer's disease patients. Protein interaction network analysis found that LYN, PTPN6 and SMAD1 could be of great value for further investigation.
It could be inferred that understanding the underlying molecular mechanism post injury, especially at early moment, may provide novel insight for development of therapeutics strategy.
本研究旨在探讨损伤后大鼠胸段固有脊髓神经元的基因表达谱。
从 GEO 数据库中下载微阵列数据集 GSE20907,包括 12 只脊髓损伤(SCI)大鼠和 12 只对照。采用 Student's t 检验鉴定 fold-change>1.2 的差异表达基因。然后,我们使用 DAVID 进行功能富集分析,以揭示功能失调的生物过程和分子特征数据库(MsigDB),以发现 SCI 基因表达特征与其他已发表基因表达特征之间的任何潜在关系。通过 STRING 构建蛋白质-蛋白质相互作用(PPI)网络,并在 Cytoscape 中可视化。通过 BinGO 对枢纽蛋白进行功能分析。
在损伤后 3 天发现基因表达谱的最大变化,并且在所有测试的时间点均发现免疫反应上调。有趣的是,损伤后 2 周上调的基因与阿尔茨海默病患者大脑中上调的基因显著重叠。蛋白质相互作用网络分析发现,LYN、PTPN6 和 SMAD1 可能具有很大的研究价值。
可以推断,了解损伤后的潜在分子机制,特别是在早期,可能为治疗策略的发展提供新的见解。