Hou Jingyi, Ouyang Yi, Deng Haiquan, Chen Zhong, Song Bin, Xie Zhongyu, Wang Peng, Li Jinteng, Li Weiping, Yang Rui
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Stem Cells Int. 2016;2016:1375031. doi: 10.1155/2016/1375031. Epub 2016 Aug 25.
Synovium-derived mesenchymal stromal cells (SMSCs) may play an important role in the pathogenesis of rheumatoid arthritis (RA) and show promise for therapeutic applications in RA. In this study, a whole-genome microarray analysis was used to detect differential gene expression in SMSCs from RA patients and healthy donors (HDs). Our results showed that there were 4828 differentially expressed genes in the RA group compared to the HD group; 3117 genes were upregulated, and 1711 genes were downregulated. A Gene Ontology analysis showed significantly enriched terms of differentially expressed genes in the biological process, cellular component, and molecular function domains. A Kyoto Encyclopedia of Genes and Genomes analysis showed that the MAPK signaling and rheumatoid arthritis pathways were upregulated and that the p53 signaling pathway was downregulated in RA SMSCs. Quantitative real-time polymerase chain reaction was applied to verify the expression variations of the partial genes mentioned above, and a western blot analysis was used to determine the expression levels of p53, p-JNK, p-ERK, and p-p38. Our study found that differentially expressed genes in the MAPK signaling, rheumatoid arthritis, and p53 signaling pathways may help to explain the pathogenic mechanism of RA and lead to therapeutic RA SMSC applications.
滑膜来源的间充质基质细胞(SMSCs)可能在类风湿关节炎(RA)的发病机制中起重要作用,并在RA的治疗应用中显示出前景。在本研究中,采用全基因组微阵列分析来检测RA患者和健康供体(HDs)的SMSCs中的差异基因表达。我们的结果显示,与HD组相比,RA组中有4828个差异表达基因;3117个基因上调,1711个基因下调。基因本体分析显示,差异表达基因在生物过程、细胞成分和分子功能域中显著富集。京都基因与基因组百科全书分析显示,RA的SMSCs中MAPK信号通路和类风湿关节炎通路上调,而p53信号通路下调。应用定量实时聚合酶链反应来验证上述部分基因的表达变化,并使用蛋白质印迹分析来确定p53、p-JNK、p-ERK和p-p38的表达水平。我们的研究发现,MAPK信号通路、类风湿关节炎和p53信号通路中的差异表达基因可能有助于解释RA的致病机制,并为RA的SMSCs治疗应用提供线索。