Abstract:
Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.
摘要:
成纤维细胞样滑膜细胞(FLS)是滑膜的重要组成部分。它们可以通过与炎性细胞的串扰和对类风湿关节炎(RA)的组织损伤途径的直接作用来促进关节损伤。最近的证据表明,与正常滑膜组织中的FLS相比,RA滑膜组织中的FLS表现出明显的代谢差异。最近的代谢组学研究表明,代谢变化,包括葡萄糖中的那些,脂质,和氨基酸代谢,在滑膜炎发作之前存在。这些变化可能是疾病早期阶段生物合成和能量需求增加的结果。活化的T细胞和一些细胞因子有助于FLS转化为具有代谢异常和促炎表型的细胞。这种转化可能是改变FLS代谢背后的潜在机制之一。靶向代谢可以抑制FLS增殖,为RA患者提供救济。在这次审查中,我们旨在总结RA中FLS代谢变化的证据,分析这些代谢改变的机制,并评价其对RA表型的影响。最后,我们旨在总结靶向FLS代谢作为未来RA有前景的治疗策略的进展和面临的挑战.