LncRNA Gm15621通过调控miR-133a/SOCS2轴抑制类风湿关节炎成纤维样滑膜细胞炎症  

LncRNA Gm15621 inhibits fibroblast-like synoviocytes inflammation by regulating miR-133a/SOCS2 axis in rheumatoid arthritis

作　　者：贾超 李树岗[1] 范秋玉 贾敏 JIA Chao;LI Shugang;FAN Qiuyu;JIA Min(Department of Rheumatology and Immunology,Wuhan N0.1 Hospital,Wuhua 430022,China;Department of General Practice,Student Health Center of Jianghan University,Wuhua 430056,China)

机构地区：[1]武汉市第一医院风湿免疫科,430022 [2]江汉大学校医院全科医学科,武汉430056

出　　处：《免疫学杂志》2021年第3期263-269,共7页Immunological Journal

摘　　要：目的探讨lncRNA Gm15621和miR-133a在类风湿关节炎滑膜组织中的表达及其与滑膜组织中成纤维样滑膜细胞炎症调控的关系。方法于2018年1月到2018年12月收集53例类风湿关节炎滑膜组织和20例正常滑膜组织,通过qPCR技术检测不同患者滑膜组织Gm15621和miR-133a的表达情况,免疫印迹法检测滑膜成纤维细胞SOCS2等蛋白的表达情况。结果类风湿关节炎患者滑膜组织Gm15461表达水平是正常滑膜组织的(43.06±2.48)%,miR-133a表达水平是正常组织的(2.94±0.13)倍;类风湿关节炎患者滑膜组织Gm15621表达水平与血清TNF-α(r=-0.441,P=0.001 1),IL-6(r=-0.442,P=0.0017)和IL-1β(r=-0.532,P<0.001)呈负相关,与滑膜组织中miR-133a(r=-0.629,P<0.001)表达呈负相关。荧光素酶报告基因显示:Gm15621和SOCS2都是miR-133a的靶基因,且miR-133a靶向抑制成纤维样滑膜细胞Gm15621和SOCS2,Gm15621抑制成纤维样滑膜细胞中miR-133a的表达。在体外,SOCS2敲低可以显著上调成纤维样滑膜细胞中TNF-α,IL-6和IL-1β的表达。结论类风湿关节炎患者滑膜组织中Gm15621低表达,miR-133a高表达,并且Gm15621通过抑制成纤维样滑膜细胞中miR-133a的表达促进SOCS2的表达,最终发挥抑制炎症因子表达的效果。This study was performed to investigate the expression effects of lncRNA Gm15621 and miR-133 a in rheumatoid arthritis(RA) synovial tissue. Herein, we collected 53 cases of rheumatoid arthritis synovial tissue and20 cases of normal synovial tissue from January 2018 to December 2018, and used qPCR to detect the expression of lncRNA Gm15621 and miR-133 a in the synovial tissue. Furthermore, Western blot was sued to detect the protein expression of SOCS2. Data showed that the expression level of Gm15461 in synovial tissue of RA patients was(43.06±2.48)% of that in normal synovial tissue, and the expression level of miR-133 a was(2.94±0.13) times that in normal tissue. The expression of Gm15621 in RA patients was negatively correlated with serum TNF-α(r=-0.441,P=0.001 1), IL-6(r=-0.442, P=0.001 7), IL-1β(r=-0.532, P<0.001) and miR-133 a expression(r=-0.629, P<0.001)in synovial tissue. The luciferase reporter gene showed that Gm15621 and SOCS2 were both target genes of miR-133 a, and miR-133 a targeted the inhibition of fibroblast-like synovial cells Gm15621 and SOCS2, while Gm15621 inhibited the expression of miR-133 a in fibroblast-like synovial cells. In vitro, SOCS2 knockdown could significantly upregulate the expression of TNF-α, IL-6 and IL-1β in fibroblast-like synoviocytes. In conclusion,Gm15621 is lowly expressed and miR-133 a is highly expressed in synovial tissue of RA patients. Gm15621 promotes the expression of SOCS2 by inhibiting the expression of miR-133 a in fibroblast-like synoviocytes, and ultimately exerts an inhibitory effect on inflammatory factor expression.

关 键 词：类风湿关节炎 长链非编码RNA 炎症 成纤维样滑膜细胞 

分 类 号：R563.8[医药卫生—呼吸系统]