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PGK1,一种葡萄糖代谢酶,可能在类风湿关节炎中发挥重要作用。

PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis.

机构信息

Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jingshi Road 16766, Jinan, Shandong, 250014, People's Republic of China.

Department of Pediatrics, Jinan Maternity and Child Care Hospital, Jianguoxiaojingsan Road 2, Jinan, Shandong, 250001, People's Republic of China.

出版信息

Inflamm Res. 2016 Oct;65(10):815-25. doi: 10.1007/s00011-016-0965-7. Epub 2016 Jun 24.

Abstract

BACKGROUND

Some 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/METHODS: Synovial tissues of collagen-induced arthritis (CIA) were analyzed with Rat Glucose Metabolism RT(2) Profiler™ 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.

RESULTS

Both 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.

CONCLUSIONS

PGK1, 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.

摘要

背景

一些研究表明,葡萄糖代谢在类风湿关节炎(RA)的发病机制中起着重要作用。本研究旨在寻找影响 RA 中葡萄糖代谢的新基因。

材料/方法:使用 Rat Glucose Metabolism RT(2) Profiler™ PCR Array 分析胶原诱导关节炎(CIA)的滑膜组织,以筛选葡萄糖代谢中具有特殊表达的基因。实时 PCR、western blot 和 ELISA 用于确认人 RA 滑膜组织和血液中的结果。用 siRNA 处理培养的滑膜成纤维细胞(RASF)以抑制靶基因的表达。进行 CCK-8 细胞增殖测定和双室 Transwell 系统,以检查处理后的 RASF 的细胞增殖和细胞迁移。

结果

PCR 阵列和实时 PCR 均检测到 CIA 大鼠滑膜组织中 ENO1、HK2 和 PGK1 的上调和 PCK1 和 PDK4 的下调。实时 PCR 和 western blot 检测到 RA 滑膜组织中 ENO1 和 PGK1 的表达增加。ELISA 检测到 RA 患者血液中 PGK1 水平较高。用抗 PGK1 siRNA 处理后,RASF 的细胞增殖和细胞迁移能力明显下降。与 TNF-α 和 IL-1α 相比,处理后的 RASF 上清液中 IL-1β 和 IFN-γ 水平显著下降。

结论

PGK1 是一种糖酵解酶,可催化 3-磷酸甘油酸转化为 2-磷酸甘油酸,在 RA 的滑膜组织和血液中表达增加,可能参与疾病的促炎和滑膜增生。

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