miRNA-451a Targets IFN Regulatory Factor 8 for the Progression of Systemic Lupus Erythematosus

被引:35
作者
Cheng, Jia [1 ,2 ]
Wu, Rui [1 ,2 ]
Long, Li [1 ,2 ]
Su, Jiang [1 ,2 ]
Liu, Jian [1 ,2 ]
Wu, Xiao-Dan [1 ,2 ]
Zhu, Jing [1 ,2 ]
Zhou, Bin [1 ,2 ]
机构
[1] Sichuan Acad Med Sci, Dept Rheumatol & Immunol, 32 West Second Sect First Ring Rd, Chengdu 610072, Sichuan, Peoples R China
[2] Sichuan Prov Peoples Hosp, 32 West Second Sect First Ring Rd, Chengdu 610072, Sichuan, Peoples R China
关键词
cytokines; IFN regulatory factor 8; immune complex deposit; miRNA-451a; systemic lupus erythematosus; SIGNALING ABNORMALITIES; DISEASE; INTERFERON; MECHANISMS; MICRORNAS; IRF8; AUTOIMMUNITY; PATHOGENESIS; INFLAMMATION; EXPRESSION;
D O I
10.1007/s10753-017-0514-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 wildtype 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.
引用
收藏
页码:676 / 687
页数:12
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