T Wen1,2, J Hou2, F Wang2, Y Zhang2, T Zhang2, T Sun2. 1. Chinese PLA Medical College, Beijing, China. 2. Department of Orthopedics, Beijing Army General Hospital, Beijing, China.
Abstract
OBJECTIVES: This study was designed to explore the molecular mechanisms of spinal cord injury (SCI) with time. METHODS: The gene expression profile (GSE45006) including four non-injured spinal cord samples as sham-control group and 20 thoracic transected spinal cords samples as experimental group at different times was downloaded from Gene Expression Omnibus database. The time-course changes of the SCI-related differentially expressed genes (DEGs) were identified. In addition, time-series expression profile clusters of DEGs were obtained, followed by gene ontology (GO) and pathway enrichment analysis of the DEGs. Moreover, the transcriptional regulatory network was constructed. RESULTS: There were 1420, 492, 743, 568 and 533 DEGs respectively at d1, d3, w1, w2 and w8 compared with that of sham group. Importantly, 101 overlapped regulated DEGs were identified at five time points and 370 collaboratively regulated genes were identified in cluster 6. Significant functions of overlapped regulated DEGs were obtained including response to wounding and developmental process. In addition, the DEGs, such as CD14 molecule (CD14) and chemokine (C-C motif) ligand 2 (CCL2), were enriched mostly in the pathways related to tuberculosis, phagosome and NF-kappa B signaling pathway. From the transcriptional regulatory network, we identified some transription factors (TFs), including member of E26 transformation-specific (ETS) oncogene family (ELK1) and zinc finger and BTB domain containing 7A (Zbtb7a). CONCLUSION: The DEGs related to immune response during SCI may provide underlying targets for treatment of SCI. Moreover, the TFs ZBTB7A and ELK1 and their target gene (dual specificity phosphatase 18 (DUSP18)) might be therapeutic targets for the treatment of SCI.
OBJECTIVES: This study was designed to explore the molecular mechanisms of spinal cord injury (SCI) with time. METHODS: The gene expression profile (GSE45006) including four non-injured spinal cord samples as sham-control group and 20 thoracic transected spinal cords samples as experimental group at different times was downloaded from Gene Expression Omnibus database. The time-course changes of the SCI-related differentially expressed genes (DEGs) were identified. In addition, time-series expression profile clusters of DEGs were obtained, followed by gene ontology (GO) and pathway enrichment analysis of the DEGs. Moreover, the transcriptional regulatory network was constructed. RESULTS: There were 1420, 492, 743, 568 and 533 DEGs respectively at d1, d3, w1, w2 and w8 compared with that of sham group. Importantly, 101 overlapped regulated DEGs were identified at five time points and 370 collaboratively regulated genes were identified in cluster 6. Significant functions of overlapped regulated DEGs were obtained including response to wounding and developmental process. In addition, the DEGs, such as CD14 molecule (CD14) and chemokine (C-C motif) ligand 2 (CCL2), were enriched mostly in the pathways related to tuberculosis, phagosome and NF-kappa B signaling pathway. From the transcriptional regulatory network, we identified some transription factors (TFs), including member of E26 transformation-specific (ETS) oncogene family (ELK1) and zinc finger and BTB domain containing 7A (Zbtb7a). CONCLUSION: The DEGs related to immune response during SCI may provide underlying targets for treatment of SCI. Moreover, the TFs ZBTB7A and ELK1 and their target gene (dual specificity phosphatase 18 (DUSP18)) might be therapeutic targets for the treatment of SCI.
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