Ji S-C, Han N, Liu Y, Li G, Sun Z, Li Z
Department of Emergency Trauma Surgery, East Hospital, Tongji University School of Medicine , Shanghai , China.
Biotech Histochem. 2015 Jul;90(5):353-60. doi: 10.3109/10520295.2015.1007481. Epub 2015 Mar 24.
Intervertebral disc degeneration is a common orthopedic disease that has been recognized as the major cause of low back pain. About 80% of the population is affected by this disease. We explored molecular mechanisms of disc degeneration and identified the genes associated with the disease. The transcription profile of GSE34095 was downloaded from Gene Expression Omnibus database with three degenerative disc samples and three healthy disc samples. Gene ontology and pathway enrichment analysis were performed. We constructed a protein-protein interaction (PPI) network and a transcription factor (TF) target network. Differentially expressed genes (DEGs) in normal and disc degeneration samples were identified including 243 up-regulated genes and 351 down-regulated genes. Meanwhile, seven Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained by mapping the 594 DEGs to the KEGG and we found that the calcium signaling pathway was the most significant for developing disc degeneration. The pathways interaction network analysis showed that the adherens junction pathway interacted with other six pathways. In addition, the top five genes, FYN, PRKCD, YWHAB, YWHAZ and AR, with a high degree of interaction of 7, 4, 4, 4 and 4, respectively, were related to the disc degeneration in the PPI network. Furthermore, transcription factors including TFAP2A, E2F4, SP3 and AR had the potential to regulate disc degeneration through the mitogen-activated protein kinase, vascular endothelial growth factor and p53 pathways. The genes and pathways that we identified may be involved in disc degeneration.
椎间盘退变是一种常见的骨科疾病，已被公认为是腰痛的主要原因。约80%的人群受该疾病影响。我们探索了椎间盘退变的分子机制，并鉴定了与该疾病相关的基因。从基因表达综合数据库下载了GSE34095的转录谱，其中包括三个退变椎间盘样本和三个健康椎间盘样本。进行了基因本体论和通路富集分析。我们构建了蛋白质-蛋白质相互作用（PPI）网络和转录因子（TF）靶标网络。鉴定了正常和椎间盘退变样本中的差异表达基因（DEG），包括243个上调基因和351个下调基因。同时，通过将594个DEG映射到京都基因与基因组百科全书（KEGG）获得了七条KEGG通路，并且我们发现钙信号通路对于椎间盘退变的发生最为显著。通路相互作用网络分析表明，黏着连接通路与其他六条通路相互作用。此外，在PPI网络中，相互作用程度分别为7、4、4、4和4的前五个基因FYN、PRKCD、YWHAB、YWHAZ和AR与椎间盘退变相关。此外，包括TFAP2A、E2F4、SP3和AR在内的转录因子有可能通过丝裂原活化蛋白激酶、血管内皮生长因子和p53通路调节椎间盘退变。我们鉴定出的基因和通路可能参与了椎间盘退变。
