Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Endocrinology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Cell Biochem. 2019 Sep;120(9):15776-15789. doi: 10.1002/jcb.28848. Epub 2019 May 9.
Traumatic brain injury (TBI) is a serious public health problem as well as a leading cause of severe posttraumatic disability. Numerous studies indicate that the differentially expressed genes (DEGs) of neural signaling pathways are strongly correlated with brain injury. To further analyze the roles of the DGEs in the central nervous system, here we systematically investigated TBI on the hippocampus and its injury mechanism at the whole genome level. On the basis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analyses, we revealed that the DEGs were involved in many signaling pathways related to the nervous system, especially neuronal survival-related pathways. Finally, we verified the microarray results and detected the gene expression of neuronal survival-related genes in the hippocampus by using real-time quantitative polymerase chain reaction. With Western blot and axon growth assay, the expression of P2rx3 was upregulated in rats subjected to TBI, and overexpression of P2rx3 promoted neurite growth of NG108 cells. Our results suggested that the DEGs (especially P2rx3) and several signaling pathways might play a pivotal role in TBI. We also provided several targeted genes related to TBI for future investigation.
创伤性脑损伤 (TBI) 是一个严重的公共卫生问题,也是严重创伤后残疾的主要原因。许多研究表明,神经信号通路的差异表达基因 (DEGs) 与脑损伤密切相关。为了进一步分析 DEGs 在中枢神经系统中的作用,我们在这里系统地研究了创伤性脑损伤对海马体的影响及其在全基因组水平上的损伤机制。基于基因本体论和京都基因与基因组百科全书分析,我们发现 DEGs 参与了许多与神经系统相关的信号通路,特别是与神经元存活相关的通路。最后,我们通过实时定量聚合酶链反应验证了微阵列结果,并检测了海马体中与神经元存活相关基因的表达。通过 Western blot 和轴突生长测定,我们发现创伤性脑损伤大鼠的 P2rx3 表达上调,而过表达 P2rx3 可促进 NG108 细胞的轴突生长。我们的结果表明,DEGs(特别是 P2rx3)和几个信号通路可能在 TBI 中发挥关键作用。我们还为未来的研究提供了几个与 TBI 相关的靶向基因。