Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
J Cell Physiol. 2020 Feb;235(2):1746-1758. doi: 10.1002/jcp.29093. Epub 2019 Jul 15.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the pathogenesis of RA is still unknown. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) are of significance in the pathogenesis of RA. In this study, three microarray profiles (GSE55457, GSE55584, and GSE55235) of human joint FLSs from 33 RA patients and 20 normal controls were extracted from the Gene Expression Omnibus Dataset and analyzed to investigate the underlying pathogenesis of RA. As analyzed by the differently expressed genes, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analysis, syndecan-4 (SDC4), a receptor of multiple cytokines and chemokines, which played a key role in the regulation of inflammatory response, was found to be an essential regulator in RA. To further validate these results, the levels of SDC4, reactive oxygen species (ROS), nitric oxide (NO), inflammation, and apoptosis in RA-FLSs were examined. SDC4-silenced RA-FLSs were also used. The results demonstrated that SDC4 and the level of ROS, NO, and inflammation were highly expressed while the apoptosis was decreased in RA-FLSs compared with normal FLSs. SDC4 silencing significantly suppressed the levels of ROS, NO, and inflammation; elevated the expression of nuclear factor erythroid 2-related factor 2; and promoted the apoptosis of RA-FLSs. Collectively, our results demonstrated a new mechanism of SDC4 in initiating the inflammation and inhibiting the apoptosis of RA-FLSs and that a potential target for the diagnosis and treatment of RA in the clinic might be developed.
类风湿关节炎（RA）是一种慢性自身免疫性炎症性疾病，其发病机制尚不清楚。类风湿关节炎成纤维样滑膜细胞（RA-FLS）在 RA 的发病机制中具有重要意义。在这项研究中，从基因表达综合数据库中提取了 33 例 RA 患者和 20 例正常对照者的人关节 FLSs 的三个微阵列图谱（GSE55457、GSE55584 和 GSE55235），并进行了分析，以探讨 RA 的潜在发病机制。通过差异表达基因、基因本体、京都基因与基因组百科全书通路富集和蛋白质-蛋白质相互作用网络分析，发现多细胞因子和趋化因子受体 syndecan-4（SDC4）在炎症反应的调节中起关键作用，是 RA 的重要调节因子。为了进一步验证这些结果，检测了 RA-FLSs 中的 SDC4、活性氧（ROS）、一氧化氮（NO）、炎症和凋亡水平。还使用了 SDC4 沉默的 RA-FLSs。结果表明，与正常 FLSs 相比，RA-FLSs 中 SDC4 及其 ROS、NO 和炎症水平表达较高，而凋亡减少。SDC4 沉默显著抑制了 ROS、NO 和炎症水平；上调核因子红细胞 2 相关因子 2 的表达；并促进 RA-FLSs 的凋亡。总之，我们的结果表明 SDC4 在引发 RA-FLSs 的炎症和抑制其凋亡方面具有新的机制，可能为临床 RA 的诊断和治疗开发出潜在的靶点。
