m6A甲基转移酶低表达与系统性红斑狼疮的关联研究  

Associations between down-regulated expression of m6A methyltransferases and systemic lupus erythematosus

作　　者：吴俊 李尚洁 张杰[2] 叶冬青 王效军 WU Jun;LI Shangjie;ZHANG Jie;YE Dongqing;WANG Xiaojun(Department of Epidemiology and Biostatistics,School of Public Health,Guangdong Medical University,Dongguan 523808,China;School of Public Health,Anhui University of Science and Technology,Hefei 231131,China)

机构地区：[1]广东医科大学公共卫生学院流行病与卫生统计学系,东莞523808 [2]安徽理工大学公共卫生学院,合肥231131

出　　处：《中华疾病控制杂志》2023年第12期1447-1454,共8页Chinese Journal of Disease Control & Prevention

基　　金：广东省基础与应用基础研究基金区域联合基金(2022A1515111042);国家自然科学基金(81872693,81872687);湛江市非资助科技攻关计划(2023B01047)。

摘　　要：目的探讨N6-甲基腺嘌呤(N6-methyladenosine,m6A)甲基转移酶与系统性红斑狼疮(systemic lupus erythematosus,SLE)的相关性。方法利用实时定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)和蛋白质印迹(western blotting,WB)实验检测m6A甲基转移酶在SLE中的表达情况,并分析其与SLE临床特征和临床用药之间关系。进一步构建m6A甲基化核心酶METTL3的干扰和过表达Jurkat细胞系,流式细胞术分析Jurkat细胞凋亡状态,RT-qPCR分析细胞因子白介素-2(interleukin-2,IL-2)和肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)分泌情况。结果m6A甲基转移酶在SLE疾病中整体低表达,其中METTL3在SLE患者T淋巴细胞中稳定下调(均P<0.05),与患者抗体和低补体等临床特征明显相关(均P<0.05)。功能实验发现,敲低METTL3会加速Jurkat细胞凋亡并增加IL-2和TNF-α表达。结论SLE中m6A甲基转移酶低表达,其中m6A甲基化核心酶METTL3可能与T淋巴细胞凋亡等稳态及炎症反应相关。m6A甲基转移酶依赖的m6A修饰在SLE中的重要作用值得进一步研究。Objective To investigate the correlation between N6-methyladenosine(m6A)methyltransferase and systemic lupus erythematosus(SLE).Methods Real-time quantitative polymerase chain reaction(RT-qPCR)and western blot(WB)were utilized to verify the expression of m6A methyltransferases in SLE,and further analyzed the associations of the expression of m6A methyltransferases with clinical characteristics and treatment of SLE.Jurkat cell lines with silencing and overexpressing METTL3 were generated for the functional investigation of T cells,flow cytometry analyzed the apoptosis and RT-qPCR detected the cytokines interleukin-2(IL-2)and tumor necrosis factor-alpha(TNF-α)secretion.Results The expression levels of m6A methyltransferases were stably down-regulated in patients with SLE,among which METTLE was stably down-regulated in T cells of patients with SLE,as well as closely correlated with antibodies(anti-dsDNA and anti-SSB/La)and low complements(all P<0.05).Functional experiments found that down-regulated expression of METTL3 inhibited the apoptosis of Jurkat cells,as well as triggered the expression of IL-2 and TNF-α.Conclusion The expression levels of m6A methyltransferases were decreased in patients with SLE,and METTL3,the core m6A methylation enzyme,may be related to T cell apoptosis and inflammatory responses.Further studies are needed to find out the important role of methyltransferase-dependent m6A modification in the prevention and treatment of SLE.

关 键 词：系统性红斑狼疮 N6-甲基腺嘌呤 METTL3 T细胞 

分 类 号：R181[医药卫生—流行病学]