关键词: 系统性红斑狼疮, 妊娠, CD4+ T细胞, miR-185, 低甲基化, 分子机制

Abstract: Objective To investigate whethermiR-185 plays a role in the pregnancy associated with SLE. Methods Real time PCR and Western blot analysis were used to investigate the role of miR-185 in aberrant methylation of T cells in SLE patients and analyze its molecular mechanism by comparing with healthy populations. Results The results revealed that 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 encodingCD11a and CD70. Inhibition of miR-185 expression in CD4+ T cells from patients with SLE caused revers effects. Conclusions This study indicated that miR-185 contributes to DNA hypo-methylation of CD4+ T cells in pregnancy patients with systemic lupus erythematosus by targeting DNA methyltransferase 1. Thus, miR-185 may represent apotential therapeutic target for SLE intervention.

Key words: Systemic lupus erythematosus, Pregnancy, miR-185, CD4+ T, Hypomethylation , Molecular Mechanisms