Hao Ming, Ji Xin-Ran, Chen Hua, Zhang Wei, Zhang Li-Cheng, Zhang Li-Hai, Tang Pei-Fu, Lu Ning
Department of Orthopedic Surgery, General Hospital of People's Liberation Army (301 Hospital), Beijing, China.
Neural Regen Res. 2018 Mar;13(3):518-527. doi: 10.4103/1673-5374.226405.
Previous studies have reported age-specific pathological and functional outcomes in young and aged patients suffering spinal cord injury, but the mechanisms remain poorly understood. In this study, we examined mice with spinal cord injury. Gene expression profiles from the Gene Expression Omnibus database (accession number GSE93561) were used, including spinal cord samples from 3 young injured mice (2-3-months old, induced by Impactor at Th9 level) and 3 control mice (2-3-months old, no treatment), as well as 2 aged injured mice (15-18-months old, induced by Impactor at Th9 level) and 2 control mice (15-18-months old, no treatment). Differentially expressed genes (DEGs) in spinal cord tissue from injured and control mice were identified using the Linear Models for Microarray data method, with a threshold of adjusted P < 0.05 and |logFC(fold change)| > 1.5. Protein-protein interaction networks were constructed using data from the STRING database, followed by module analysis by Cytoscape software to screen crucial genes. Kyoto encyclopedia of genes and genomes pathway and Gene Ontology enrichment analyses were performed to investigate the underlying functions of DEGs using Database for Annotation, Visualization and Integrated Discovery. Consequently, 1,604 and 1,153 DEGs were identified between injured and normal control mice in spinal cord tissue of aged and young mice, respectively. Furthermore, a Venn diagram showed that 960 DEGs were shared among aged and young mice, while 644 and 193 DEGs were specific to aged and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in osteoclast differentiation, extracellular matrix-receptor interaction, nuclear factor-kappa B signaling pathway, and focal adhesion. Unique genes for aged and young injured groups were involved in the cell cycle (upregulation of PLK1) and complement (upregulation of C3) activation, respectively. These findings were confirmed by functional analysis of genes in modules (common, 4; aged, 2; young, 1) screened from protein-protein interaction networks. Accordingly, cell cycle and complement inhibitors may be specific treatments for spinal cord injury in aged and young mice, respectively.
先前的研究报告了年轻和老年脊髓损伤患者特定年龄的病理和功能结果，但其机制仍知之甚少。在本研究中，我们对脊髓损伤小鼠进行了检查。使用了来自基因表达综合数据库（登录号GSE93561）的基因表达谱，包括3只年轻损伤小鼠（2 - 3个月大，由撞击器在胸9水平诱导损伤）和3只对照小鼠（2 - 3个月大，未处理）的脊髓样本，以及2只老年损伤小鼠（15 - 18个月大，由撞击器在胸9水平诱导损伤）和2只对照小鼠（15 - 18个月大，未处理）的脊髓样本。使用微阵列数据的线性模型方法鉴定损伤小鼠和对照小鼠脊髓组织中的差异表达基因（DEG），阈值为调整后P < 0.05且|logFC（倍数变化）| > 1.5。使用STRING数据库的数据构建蛋白质 - 蛋白质相互作用网络，随后通过Cytoscape软件进行模块分析以筛选关键基因。使用注释、可视化和综合发现数据库进行京都基因与基因组百科全书通路和基因本体富集分析，以研究DEG的潜在功能。结果，在老年和年轻小鼠的脊髓组织中，分别在损伤小鼠和正常对照小鼠之间鉴定出1604个和1153个DEG。此外，维恩图显示老年和年轻小鼠共有960个DEG，而分别有644个和193个DEG是老年和年轻小鼠特有的。功能富集表明，共享的DEG参与破骨细胞分化、细胞外基质 - 受体相互作用、核因子 - κB信号通路和粘着斑。老年和年轻损伤组的独特基因分别参与细胞周期（PLK1上调）和补体（C3上调）激活。这些发现通过对从蛋白质 - 蛋白质相互作用网络筛选出的模块（共同模块4个；老年模块2个；年轻模块1个）中的基因进行功能分析得到证实。因此，细胞周期抑制剂和补体抑制剂可能分别是老年和年轻小鼠脊髓损伤的特异性治疗方法。
