关键词: 神经再生, 脊髓损伤, 老年的, 年轻的, 转录组, 差异表达基因, PPI网络, 功能富集, 炎症, 细胞周期, 补体

Abstract:

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.

Key words: nerve regeneration, spinal cord injury, aged, young, transcriptome, differentially expressed genes, protein–protein interaction network, function enrichment, inflammation, cell cycle, complement, neural regeneration