Fukuda Koji, Miura Yasushi, Maeda Toshihisa, Hayashi Shinya, Matsumoto Tomoyuki, Kuroda Ryosuke
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.
Division of Orthopedic Science, Department of Rehabilitation Science, Kobe University Graduate School of Health Science, Kobe, Hyogo 654-0142, Japan.
Exp Ther Med. 2021 Sep;22(3):1000. doi: 10.3892/etm.2021.10432. Epub 2021 Jul 15.
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in synovial tissues. Hyperplasia of synovial tissues leads to the formation of pannus that invades the joint cartilage and bone, resulting in joint destruction. Fas ligand (FasL), which is a member of the tumor necrosis factor superfamily, contributes to the pathogenesis of autoimmune diseases, including RA. The current study attempted to identify genes whose expressions in rheumatoid fibroblast-like synoviocytes (RA-FLS) were regulated by FasL, using cDNA microarray. A total of four individual lines of primary cultured RA-FLS were incubated either with recombinant human FasL protein or PBS as an unstimulated control for 12 h. Gene expression was detected using a microarray assay. The results revealed the expression profiles of genes in RA-FLS regulated by Fas and investigated the functions of the genes that were regulated. Among the genes in this profile, the mRNA expression changes of the following genes were indicated to be of note using RT-qPCR: Dual specificity phosphatase 6, epiregulin, interleukin 11, angiopoietin-like 7, protein inhibitor of activated STAT 2 and growth differentiation factor 5. These genes may affect the pathogenesis of RA by affecting apoptosis, proliferation, cytokine production, cytokine-induced inflammation, intracellular signaling, angiogenesis, bone destruction and chondrogenesis. To the best of our knowledge, the current study is the first study to reveal the expression profile of genes in RA-FLS regulated by FasL. The data demonstrated that FasL may regulate the expression of a number of key molecules in RA-FLS, thus affecting RA pathogenesis. Further studies of the genes detected may improve the understanding of RA pathogenesis and provide novel treatment targets for RA.
类风湿关节炎(RA)是一种自身免疫性疾病,可导致滑膜组织慢性炎症。滑膜组织增生会导致血管翳形成,血管翳侵入关节软骨和骨骼,从而导致关节破坏。Fas配体(FasL)是肿瘤坏死因子超家族的成员之一,在包括RA在内的自身免疫性疾病发病机制中起作用。本研究试图利用cDNA微阵列鉴定类风湿成纤维样滑膜细胞(RA-FLS)中其表达受FasL调控的基因。将总共四株原代培养的RA-FLS分别用重组人FasL蛋白或作为未刺激对照的PBS孵育12小时。使用微阵列分析检测基因表达。结果揭示了Fas调控的RA-FLS中基因的表达谱,并研究了受调控基因的功能。在该谱中的基因中,使用RT-qPCR表明以下基因的mRNA表达变化值得关注:双特异性磷酸酶6、表皮调节素、白细胞介素11、血管生成素样7、活化STAT 2蛋白抑制剂和生长分化因子5。这些基因可能通过影响细胞凋亡、增殖、细胞因子产生、细胞因子诱导的炎症、细胞内信号传导、血管生成、骨破坏和软骨形成来影响RA的发病机制。据我们所知,本研究是首次揭示FasL调控的RA-FLS中基因表达谱的研究。数据表明,FasL可能调控RA-FLS中许多关键分子的表达,从而影响RA发病机制。对检测到的基因进行进一步研究可能会增进对RA发病机制的理解,并为RA提供新的治疗靶点。