中文摘要：

微小RNA（microRNA,miRNA）作为一种基因表达调控因子,在自身免疫性疾病中起重要作用。本研究旨在研究系统性红斑狼疮（SLE）患者中低表达的miR-125a基因在SLE炎症反应中的作用及其可能的作用机制。通过miRNA Taqman荧光定量聚合酶链反应（RT-PCR）,发现同正常对照组相比,miR-125a表达水平在SLE患者中明显降低。生物信息学分析发现T淋巴细胞激活晚期促进RANTES分泌的主要转录因子KLF13是miR-125a的潜在靶基因。定量结果也表明,SLE患者中KLF13和RANTES水平正相关。从基因组DNA中克隆pri-miR-125a基因,构建miR-125a的表达载体。在HeLa细胞中过表达miR-125a能抑制内源性KLF13 mRNA的表达,反之亦然。报告基因系统实验证实,miR-125a能直接作用于KLF13的3′UTR区,从而调节KLF13的表达。进一步发现过表达miR-125a可以降低狼疮T细胞分泌RANTES的水平。我们的研究表明,miR-125a通过调节转录因子KLF13的表达而调节参与狼疮发病的炎性趋化因子RANTES的分泌。这提示定向干预miR-125a的表达水平可调节炎症性趋化因子RANTES的表达,从而发展为SLE新的治疗手段。

英文摘要：

Recent studies have implicated that microRNAs（miRNAs） contribute to the autoimmune diseases as a post-transcriptional modulators.In this study,we further investigated how the lower expression of miR-125a gene in patients with SLE would contribute to the dysregulation of inflammatory chemokines.It was found that the expression of miR-125a in SLE patients was significantly decreased compared with the healthy controls by using Taqman real time quantitative PCR.Bioinformatic algorithms predicted that KLF13,a key transcription factor regulated＂late＂expression of RANTES in T lymphocytes,and it could be served as a candidate target of miR-125a.Meanwhile,a positive correlation was found between KLF13 and RANTES expression.Furthermore,the endogenous expression of KLF13 mRNA was reduced or increased in a dose-dependent manner following miR-125a over-expression or inhibition,respectively.The reporter gene assays also approved that miR-125a directly targeted the 3＇UTR of KLF13.We found that miR-125a potentially alleviated high levels of RANTES in T cells from SLE patients,and it was down-regulated in SLE compared with healthy individuals.It is evident that restoration of the miR-125a expression in lupus patients may help to reduce RANTES expression and provide a new target for treatment or prevention of lupus.