Can Metabolic Pathways Be Therapeutic Targets in Rheumatoid Arthritis?
Can Metabolic Pathways Be Therapeutic Targets in Rheumatoid Arthritis?
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DOI：
10.3390/jcm8050753
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发表时间：
2019-05
影响因子：
3.9
通讯作者：
E. Sanchez-Lopez;An-Chieh Cheng;M. Guma
中科院分区：
文献类型：
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作者：
E. Sanchez-Lopez;An-Chieh Cheng;M. Guma
肿瘤细胞和免疫细胞的代谢重组已被视为新的药物靶点的有前途的来源。类风湿性关节炎（RA）中涉及的许多分子途径直接改变滑膜代谢，并将驻留细胞（如成纤维细胞样滑膜细胞（FLS）和滑膜组织巨噬细胞（STM））转化为降解软骨和骨的酶和促进免疫细胞浸润的细胞因子的过度产生。最近的研究表明，RA患者的基质细胞和免疫细胞发生代谢变化。滑膜中的代谢破坏提供了使用基于体内代谢的成像技术进行患者分层和监测治疗反应的机会。此外，这些代谢变化可能是治疗靶向的。因此，重置滑膜的代谢为RA的疾病调节和稳态恢复提供了额外的机会。事实上，风湿病学家已经使用抗代谢药物甲氨蝶呤（一种化疗药物）治疗炎症性关节炎患者。不损害全身稳态或正常细胞中相应代谢功能的代谢靶点可以增加风湿性疾病的药物配置，用于独立于全身免疫抑制的联合治疗。本文总结了什么是已知的代谢在滑膜组织细胞和重点化疗的目标代谢作为潜在的未来治疗策略类风湿关节炎。
The metabolic rewiring of tumor cells and immune cells has been viewed as a promising source of novel drug targets. Many of the molecular pathways implicated in rheumatoid arthritis (RA) directly modify synovium metabolism and transform the resident cells, such as the fibroblast-like synoviocytes (FLS), and the synovial tissue macrophages (STM), toward an overproduction of enzymes, which degrade cartilage and bone, and cytokines, which promote immune cell infiltration. Recent studies have shown metabolic changes in stromal and immune cells from RA patients. Metabolic disruption in the synovium provide the opportunity to use in vivo metabolism-based imaging techniques for patient stratification and to monitor treatment response. In addition, these metabolic changes may be therapeutically targetable. Thus, resetting metabolism of the synovial membrane offers additional opportunities for disease modulation and restoration of homeostasis in RA. In fact, rheumatologists already use the antimetabolite methotrexate, a chemotherapy agent, for the treatment of patients with inflammatory arthritis. Metabolic targets that do not compromise systemic homeostasis or corresponding metabolic functions in normal cells could increase the drug armamentarium in rheumatic diseases for combination therapy independent of systemic immunosuppression. This article summarizes what is known about metabolism in synovial tissue cells and highlights chemotherapies that target metabolism as potential future therapeutic strategies for RA.