Li Jia-He, Shi Zhong-Ju, Li Yan, Pan Bin, Yuan Shi-Yang, Shi Lin-Lin, Hao Yan, Cao Fu-Jiang, Feng Shi-Qing
Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.
Department of Orthopedics, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
Neural Regen Res. 2020 Jan;15(1):103-111. doi: 10.4103/1673-5374.264460.
Zebrafish and human genomes are highly homologous; however, despite this genomic similarity, adult zebrafish can achieve neuronal proliferation, regeneration and functional restoration within 6-8 weeks after spinal cord injury, whereas humans cannot. To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury, and to explore the key genes and pathways of axonal regeneration after spinal cord injury, microarray GSE56842 was analyzed using the online tool, GEO2R, in the Gene Expression Omnibus database. Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes. Finally, we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals. A total of 636 differentially expressed genes were obtained, including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained. A protein-protein interaction network contained 480 node genes and 1976 node connections. We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score. The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish. Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish. Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells, such as Schwann cells or neural progenitor cells, after spinal cord injury in zebrafish. Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish, providing targets for treatment of spinal cord injury in mammals.
斑马鱼和人类基因组高度同源；然而，尽管有这种基因组相似性，成年斑马鱼在脊髓损伤后6 - 8周内能够实现神经元增殖、再生和功能恢复，而人类则不能。为了分析脊髓损伤后轴突再生神经元和轴突未再生神经元之间斑马鱼基因的差异表达，并探索脊髓损伤后轴突再生的关键基因和途径，我们使用在线工具GEO2R在基因表达综合数据库中分析了微阵列GSE56842。基因本体论和蛋白质 - 蛋白质相互作用网络用于分析鉴定出的差异表达基因。最后，我们筛选了可能在斑马鱼和哺乳动物脊髓损伤修复中起作用的基因和途径。共获得636个差异表达基因，其中轴突再生神经元中有255个上调和381个下调的差异表达基因。还获得了基因本体论和京都基因与基因组百科全书富集结果。一个蛋白质 - 蛋白质相互作用网络包含480个节点基因和1976个节点连接。我们还获得了相关性最高的10个枢纽基因和得分最高的两个模块。结果表明，血影蛋白可能促进斑马鱼脊髓损伤后的轴突再生。转化生长因子β信号通路可能抑制斑马鱼脊髓损伤后的修复。粘着斑或紧密连接可能在斑马鱼脊髓损伤后某些细胞（如施万细胞或神经祖细胞）的迁移和增殖中起重要作用。生物信息学分析确定了斑马鱼脊髓损伤后轴突再生中的关键候选基因和途径，为哺乳动物脊髓损伤的治疗提供了靶点。
