Department of Medicine, University of Otago, Christchurch, New Zealand.
J Rheumatol. 2013 Sep;40(9):1519-22. doi: 10.3899/jrheum.130066. Epub 2013 Jul 15.
To determine whether methotrexate (MTX) affects the expression of genes involved in the transport [SLC19A1 (RFC1), ABCB1 (MDR1), ABCC1 (multidrug resistance proteins 1), ABCG2 (BCRP)], metabolism [γ-glutamyl hydrolase (GGH), folylpolyglutamate synthetase (FPGS)], and mechanism of action of MTX [thymidylate synthase, MTR, MTRR] in rheumatoid synovium.
Synovial tissue samples were obtained from 20 patients with rheumatoid arthritis (RA). Gene expression was undertaken using quantitative real-time PCR.
All the genes examined were expressed in all samples. Expression of SLC19A1, GGH, FPGS, ABCC1, and MTRR was significantly higher in patients receiving MTX compared to those not receiving MTX (p < 0.05). The ratio of FPGS:GGH gene expression was 2.7 ± 0.51 ng/ml GAPDH (range 0.67-9.58).
Genes involved in the transport, metabolism, and mechanism of action of MTX are expressed in rheumatoid joint synovium. These data provide evidence that MTX has the potential to be polyglutamated within the joint. The higher expression of FPGS compared to GGH in synovial tissue might favor production of long-chain MTX polyglutamates. Thus MTX has the potential to exert its therapeutic effects at the primary site of the inflammatory process in RA.
确定甲氨蝶呤（MTX）是否影响参与转运[SLC19A1（RFC1）、ABCB1（MDR1）、ABCC1（多药耐药蛋白 1）、ABCG2（BCRP）]、代谢[γ-谷氨酰水解酶（GGH）、叶酸多聚谷氨酸合成酶（FPGS）]和 MTX 作用机制[胸苷酸合成酶、MTR、MTRR]的基因在类风湿滑膜中的表达。
从 20 例类风湿关节炎（RA）患者中获取滑膜组织样本。采用实时定量 PCR 进行基因表达检测。
所有被检测的基因在所有样本中均有表达。与未接受 MTX 治疗的患者相比，接受 MTX 治疗的患者 SLC19A1、GGH、FPGS、ABCC1 和 MTRR 的表达显著升高（p<0.05）。FPGS:GGH 基因表达比值为 2.7±0.51ng/mlGAPDH（范围 0.67-9.58）。
参与 MTX 转运、代谢和作用机制的基因在类风湿关节滑膜中表达。这些数据提供了证据表明 MTX 有可能在关节内聚谷氨酸化。与 GGH 相比，滑膜组织中 FPGS 的高表达可能有利于长链 MTX 聚谷氨酸的产生。因此，MTX 有可能在 RA 的炎症过程的主要部位发挥其治疗作用。
