miRNA-185和DNA甲基转移酶1在妊娠合并系统性红斑狼疮患者T细胞中的表达及其意义  

Expression and significance of miRNA-185 in T cells of pregnant patients with systemic lupus erythematosus

作　　者：刘恩令[1] 刘铮[2] 周玉秀[3] 李君[1] 张冬红 蔡朝辉[1] 王立群[1] 陈梅[1] 郑寰宇[1] En-ling Liu;Zheng Liu;Yu-xiu Zhou;Jun Li;Dong-hong Zhang;Zhao-hui Cai;Li-qun Wang;Mei Chen;Huan-yu Zheng(The department of Obstetrics and Gynecology,Tangshan Gongren Hospital Affiliated to Hebei Medical University,Tangshan,Hebei 063000,China;Department of Rheumatology and Immunology,General Hospital Affiliated to Tianjin Medical University,Tianjin 300052,China;The department of Rheumatology and Immunology,Tangshan Gongren Hospital Affiliated to Hebei Medical University,Tangshan,Hebei 063000,China)

机构地区：[1]河北医科大学附属唐山市工人医院妇产科,河北唐山063000 [2]天津医科大学总医院风湿免疫科,天津300052 [3]河北医科大学附属唐山市工人医院风湿免疫科,河北唐山063000

出　　处：《中国现代医学杂志》2018年第33期35-39,共5页China Journal of Modern Medicine

基　　金：河北省科技厅重点研究项目(No:162777190)

摘　　要：目的探讨miRNA-185和DNA甲基转移酶1(DNMT1)在妊娠合并系统性红斑狼疮(SLE)患者T细胞中的表达及在发病中的作用。方法采用实时荧光定量聚合酶链反应和蛋白质印迹检测DNMT1mRNA和蛋白的表达,核转染后72 h检测甲基化敏感性基因的水平。并与健康人群比较,分析其表达差异及意义。结果结果显示,miRNA-185在妊娠合并SLE患者的CD4^+T细胞中上调(P <0.05),其过表达与DNMT1 mRNA水平呈负相关。在健康人CD4^+T细胞中,miRNA-185的过表达会导致DNA低甲基化、CD11a和CD70基因编码的上调。抑制SLE患者的CD4^+T细胞中miRNA-185的表达,会起到DNA甲基化逆转作用。结论 miRNA-185能靶向作用于DNMT1,并导致系统性红斑狼疮患者妊娠期间CD4^+T细胞的DNA低甲基化。miRNA-185可能是SLE干预治疗的潜在治疗靶点。Objective To investigate expression of miRNA-185 and DNA methyltransferase 1(DNMT1)in T cells of pregnant patients with systemic lupus erythematosus(SLE)and potential clinical significance.Methods Expression of miRNA-185 and DNMT1 in T cells was measured by qRT-PCR and Western blot.Methylation level of T cells in SLE patients was determined.Results Expression of miRNA-185 was upregulated significantly in CD4+T cells from patients,which was negatively correlated with DNA methyltransferase 1(DNMT1)mRNA levels.Overexpression of miRNA-185 in CD4+T cells from healthy donors led to the DNA hypomethylation and up-regulation of CD11a and CD70 genes.Inhibition of miRNA-185 expression in CD4+T cells from patients with SLE caused reverse effects.Target prediction analysis and dual luciferase reporter assays confirmed that DNMT1 was a direct target of miRNA-185.Conclusions This study indicates that miRNA-185 contributes to DNA hypomethylation in CD4+T cells of pregnant patients with SLE by targeting DNMT1,which may represent a potential therapeutic target for SLE.

关 键 词：系统性红斑狼疮 妊娠 CD4+T细胞 miRNA-185 DNA甲基转移酶1 表达 

分 类 号：R593.24[医药卫生—内科学]