系统性红斑狼疮患者中miR-146a表达缺陷与I型干扰素通路过度活化相关

Ι型干扰素(IFN)通路过度活化与固有免疫反应异常在系统性红斑狼疮(SLE)发病中起重要作用。miR-146a作为一个负调控因子,在固有免疫应答中发挥重要作用。为探索miR-146a在SLE发病中的作用,通过实时荧光定量聚合酶链反应技术检测18例SLE患者和11例正常对照miR-146a的表达,发现同正常对照组相比,miR-146a表达水平在SLE患者中明显降低,SLE活动组中下降则更加明显;同时检测miR-146a的靶基因IRAK1和TRAF6 mRNA表达,发现在SLE患者中其水平显著高于正常对照组;进一步分析miR-146a与IFN诱导基因表达之间的关系,结果显示两者之间存在负相关,体外实验也证实miR-146a能够负向调节I型干扰素通路。综上所述,我们的研究结果提示miR-146a可能作为一个新的生物标志物,SLE患者中miR-146a表达水平下降,导致I型干扰素通路负调控作用被削弱,从而参与疾病的发生发展。

Correlation of the defective expression of miR-146a and the over-activation of type I interferon pathway

Over-activation of type I interferon pathway and dysfunction of the innate immune system play pivotal role in the pathogenesis of systemic lupus erythematosus(SLE),and previous studies had demonstrated that the microRNA miR-146a could act as a negative regulator in innate immunity.To investigate the possible mechanism of miR-146a in the pathogenesis of SLE,the expression of miR-146a of 18 patients with SLE and 11 healthy individuals was assayed by Taqman real time quantitative PCR.In comparison with those of the healthy controls,it was found that the expression of miR-146a in SLE patients was significantly reduced and this reduction was even more prominent in cases with active SLE than those with inactive one.Meanwhile,SYBR green real-time quantitative PCR was used to evaluate the mRNA expression levels of target genes TRAF6 and TRAK1 of miR-146a.The expression levels of TRAK6 and TRAK1 mRNA were significantly higher than those of the healthy controls.Furthermore,the expression level of miR-146a was negatively correlated with the interferon score.As demonstrated by reporter gene assay,over-expression of miR-146a could impair the activity of ISRE reporter gene.From these results,it is possible that defective expression of miR-146a may contribute to abonormal activation of type 1 IFN pathway,thus participating to the pathogenesis of SLE.