Department of Rheumatology & Immunology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, No.32 West Second Section First Ring Road, Chengdu, 610072, Sichuan, China.
Inflammation. 2017 Apr;40(2):676-687. doi: 10.1007/s10753-017-0514-8.
Increasing evidence has shown that miRNA-451a (miR-451a) is associated with the development of systemic lupus erythematosus (SLE); however, the mechanism of this association is not fully known. The present study found an increased expression of miR-451a in the spleen and thymus of an SLE mice model. A decrease in miR-451a expression partly relieved the enlargement of the spleen and decreased the proteinuria content and immune complex deposits. The deficiency in miR-451a also decreased numbers of CD4+CD69+ and CD4+/CD8+ T cells and the levels of the serum cytokines IL-17a and IL-4. The IFN regulatory factor (IRF) 8 was highly expressed in the immune organs of wild-type mice but was suppressed in SLE-like mice. A dual-luciferase reporter assay was carried out in combination with gene silencing and overexpression to verify that IRF8 was a target of miR-451a in vitro and in vivo. The data indicate the function and a target of miR-451a in SLE, providing a new target for SLE therapy.
越来越多的证据表明，miRNA-451a（miR-451a）与系统性红斑狼疮（SLE）的发展有关；然而，这种关联的机制尚不完全清楚。本研究发现，SLE 小鼠模型的脾脏和胸腺中 miR-451a 的表达增加。miR-451a 表达的降低部分缓解了脾脏肿大，并降低了蛋白尿含量和免疫复合物沉积。miR-451a 的缺乏还减少了 CD4+CD69+和 CD4+/CD8+T 细胞的数量以及血清细胞因子 IL-17a 和 IL-4 的水平。干扰素调节因子（IRF）8 在野生型小鼠的免疫器官中高度表达，但在狼疮样小鼠中受到抑制。通过双荧光素酶报告基因检测结合基因沉默和过表达实验，在体外和体内验证了 IRF8 是 miR-451a 的靶基因。这些数据表明了 miR-451a 在 SLE 中的作用和靶基因，为 SLE 的治疗提供了新的靶点。
