miR-185在妊娠合并系统性红斑狼疮患者的T细胞异常甲基化中的作用及分子机制  

Role and molecular mechanism of miR-185 in aberrant methylation of T cells in pregnancy patients with systemic lupus erythematosus

作　　者：刘恩令[1] 刘铮[2] 周玉秀[3] 张冬红 陈梅[1] LIU En-lingl;LIU Zheng;ZHOU Yu-xiu;ZHANG Dong-hong;CHEN Mei(Dept.of Obstetrics and Gynecology,Tangshan Gongren Hospital Affiliated to Hebei Medical University,Tangshan 063000;Dept.of Rheumatology and Immunology,General Hospital Affiliated to Tianjin Medical University,Tianjin 300052;Dept.of Rheumatology and Immunology,Tangshan Gongren Hospital Affiliated to Hebei Medical University,Tangshan 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：《基础医学与临床》2018年第9期1280-1285,共6页Basic and Clinical Medicine

基　　金：河北省科技厅重点研究项目(162777190)

摘　　要：目的探讨miR-185是否在妊娠合并系统性红斑狼疮(SLE)患者中有重要作用。方法采用实时定量PCR和蛋白质印迹等分子生物学技术对miR-185在SLE患者的T细胞异常甲基化中所起的作用进行研究,并与健康人群对比,分析其可能的分子机制。结果 miR-185在妊娠合并SLE患者的CD4+T细胞中显著上调,其过表达与DNA甲基转移酶1(DNMT1)mRNA水平呈负相关。miR-185靶基因预测分析和双荧光素酶报告实验结果证实,DNMT1是miR-185的直接作用靶标。而且,在健康人CD4+T细胞中,miR-185的过表达会导致DNA低甲基化、编码CD11a和CD70的基因上调。抑制SLE患者的CD4+T细胞中miR-185的表达,会产生DNA甲基化逆转作用。结论 miR-185通过靶向作用于DNMT1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。miR-185可能是SLE干预治疗的潜在治疗靶点。Objective To investigate whether miR-185 plays a role in the pregnancy associated with systemic lupus erythematosus（ SLE）. Methods Real time PCR and Western blot were used to investigate the role of miR-185 in aberrant methylation of T cells in SLE patients and to analyze its molecular mechanism by comparing with healthy populations. Results miR-185 was significantly upregulated in CD4^＋T cells from patients with pregnancy complicated with SLE and its degree of over-expression was inversely correlated with DNA methyltransferase 1（ DNMT1） mRNA levels. Target gene of miR-185 prediction analysis and dualluciferase reporter assays confirmed that DNMT1 was a direct target of miR-185. Furthermore,over-expression of miR-185 in CD4^＋T cells from healthy donors led to the DNA hypo-methylation and up-regulation of genes encoding CD11 a and CD70. Inhibition of miR-185 expression inCD4^＋T cells from patients with SLE caused revers effects. Conclusions miR-185 contributes to DNA hypo-methylation of CD4^＋T cells in pregnancy patients with SLE by targeting DNA methyltransferase 1. miR-185 may be a potential therapeutic target for SLE treatment.

关 键 词：系统性红斑狼疮 妊娠 miR-185 CD4^+T细胞 低甲基化 

分 类 号：R73[医药卫生—肿瘤]