PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis
PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis
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PGK1是一种葡萄糖代谢酶，可能在类风湿性关节炎中发挥重要作用
DOI：
10.1007/s00011-016-0965-7
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发表时间：
2016
影响因子：
6.7
通讯作者：
Chang Xiaotian
中科院分区：
文献类型：
--
作者：
Zhao Yan;Yan Xinfeng;Li Xia;Zheng Yabing;Li Shufeng;Chang Xiaotian
背景研究表明糖代谢在类风湿关节炎（RA）的发病机制中起重要作用。本研究旨在寻找影响RA糖代谢的新基因。材料/方法采用大鼠葡萄糖代谢RT 2 Profiler ™ PCR芯片对胶原诱导性关节炎（CIA）滑膜组织进行分析，筛选在糖代谢中特异表达的基因。采用Real-time PCR、Western blotting、ELISA等方法对RA患者滑膜组织和血液进行检测。用siRNA处理培养的滑膜成纤维细胞（RASF）以抑制靶基因的表达。CCK-8细胞增殖实验和transwell双室系统检测细胞增殖和细胞迁移。结果PCR芯片和实时荧光定量PCR均检测到CIA大鼠滑膜组织中ENO 1、HK 2和PGK 1表达上调，而PCK 1和PDK 4表达下调。Real-time PCR和Western blotting检测到RA滑膜组织中ENO 1和PGK 1的表达增加。ELISA检测到RA患者血液中高水平的PGK 1。在抗PGK 1 siRNA处理后，在RASF中显著检测到细胞增殖和细胞迁移能力降低。结论PGK 1是一种催化3-磷酸甘油酸转化为2-磷酸甘油酸的糖酵解酶，在RA滑膜组织和血液中表达增加，可能参与了RA的促炎症和滑膜增生过程。
BackgroundSome studies have indicated that glucose metabolism plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to find the novel genes affecting glucose metabolism in RA.Materials/methodsSynovial tissues of collagen-induced arthritis (CIA) were analyzed with Rat Glucose Metabolism RT2Profiler™ PCR Array to screen those genes with special expressions in glucose metabolism. Real-time PCR, western blotting, and ELISA were used to confirm the result in synovial tissues and blood of human RA. Culture synovial fibroblast cells (RASF) was treated with siRNA to suppress expressions of the target genes. CCK-8 cell proliferation assay and two-compartment transwell system were performed to examine cell proliferation and cell migration of the treated RASF.ResultsBoth PCR array and real-time PCR detected the up-regulation of ENO1, HK2, and PGK1 and the down-regulation of PCK1 and PDK4 in synovial tissues of CIA rats. Real-time PCR and western blotting detected the increased expression of ENO1 and PGK1 in RA synovial tissues. ELISA detected a high level of PGK1 in the blood of RA patients. Decreased cell proliferation and cell migration capabilities were significantly detected in RASF following treatment of anti-PGK1 siRNA. IL-1β and IFN-γ rather than TNF-α and IL-1α levels were significantly declined in supernatants of the treated RASF.ConclusionsPGK1, a glycolytic enzyme catalyzing the conversion of 3-phosphoglycerate into 2-phosphoglycerate, has increased expression in synovial tissues and blood of RA, which may be involved in pro-inflammation and synovial hyperplasia of the disease.