MicroRNA-26a negatively regulates toll-like receptor 3 expression of rat macrophages and ameliorates pristane induced arthritis in rats.
MicroRNA-26a negatively regulates toll-like receptor 3 expression of rat macrophages and ameliorates pristane induced arthritis in rats.
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MicroRNA-26a 负向调节大鼠巨噬细胞 Toll 样受体 3 的表达并改善降植烷诱导的大鼠关节炎
DOI：
10.1186/ar4435
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发表时间：
2014-01-14
影响因子：
4.9
通讯作者：
Lu S
中科院分区：
文献类型：
--
作者：
Jiang C;Zhu W;Xu J;Wang B;Hou W;Zhang R;Zhong N;Ning Q;Han Y;Yu H;Sun J;Meng L;Lu S
Toll样受体（TLR）3信号异常在实验性类风湿关节炎和人类类风湿关节炎的发病机制中起着不可或缺的作用，microRNAs（miRNAs）可能参与了这一信号通路的调控。方法采用双荧光素酶报告基因技术，检测miR-26 a与TLR 3之间的相互作用，并观察miR-26 a模拟物对降植烷诱导的大鼠关节炎（PIA）的影响。将miR-26 a模拟物和抑制剂转染大鼠巨噬细胞NR 8383后，采用RT-qPCR和Western blotting检测miR-26 a对TLR 3基因表达的调节作用。用Poly I：C（TLR 3配体）阻断TLR 3的激活，并检测其下游细胞因子干扰素（IFN）-β和肿瘤坏死因子（TNF）-α的mRNA表达，以确定TLR 3信号通路的调控。在大鼠骨髓源性巨噬细胞（BMDM）诱导过程中、降植烷刺激的NR 8383细胞和甲氨蝶呤（MTX）处理的PIA大鼠脾脏中检测TLR 3和miR-26 a的表达。将miR-26 a模拟物腹腔注射给PIA大鼠，通过肉眼或显微镜观察评估关节炎的严重程度。通过转染miR-26 a模拟物和抑制剂修饰miR-26 a功能，在NR 8383细胞中表现出相应的TLR 3及其信号下游细胞因子表达的抑制和增强。BMDM诱导过程中miR-26 a的表达变化与TLR 3的表达呈负相关。此外，这两种异常表达在MTX治疗的关节炎大鼠脾脏中被挽救。结论miR-26 a通过靶向调节大鼠巨噬细胞中的TLR 3信号通路，抑制了TLR 3的表达，为研究实验性关节炎中TLR 3的异常表达提供了新的思路。
IntroductionAbnormal toll-like receptor (TLR)3 signaling plays an indispensable role in pathogenesis of both experimental and human rheumatoid arthritis, and microRNAs (miRNAs) might orchestrate this signaling pathway. This study was performed to determine the relationship between miR-26a andTLR3in rat macrophages and to observe effects of miR-26a mimic on pristane induced arthritis (PIA) in rats.MethodsDual luciferase reporter assay was used to validate the direct interaction between miR-26a (a candidate miRNA to targettlr3mRNA) andtlr33′UTR. MiR-26a regulation onTLR3gene expression was determined using RT-qPCR and Western blotting after miR-26a mimics and inhibitors were transfected into rat macrophage line NR8383 cells. Poly I:C (TLR3ligand) was used to triggerTLR3activation, and mRNA expression of its downstream cytokines interferon (ifn)-β and tumor necrosis factor (tnf)-α was accordingly detected to determine the regulation of TLR3 signaling. Expressions ofTLR3and miR-26a were detected during rat bone marrow derived macrophage (BMDM) induction, in pristane stimulated NR8383 cells and spleens from methotrexate (MTX) treated PIA rats. A miR-26a mimic was administrated intraperitoneally to PIA rats, and arthritis severity was evaluated by macroscopic or microscopic observations.ResultsDirect target relationship between miR-26a andtlr3mRNA in rats was confirmed. Modifications of miR-26a function by transfection of miR-26a mimics and inhibitors exhibited corresponding repression and augmentation ofTLR3and its signaling downstream cytokine expressions in NR8383 cells. The alteration of miR-26a expression was negatively related withTLR3expression during BMDM induction, in pristane-primed NR8383 cells and PIA rat spleens. Moreover, both abnormal expressions were rescued in MTX treated arthritis rat spleens. The miR-26a mimic treatment displayed the depression ofTLR3expression and ameliorated the disease severity in the rats with pristane induced arthritis.ConclusionsMiR-26a negatively regulatesTLR3signaling via targeting ofTLR3itself in rat macrophages, and this finding provides a novel insight into abnormalTLR3overexpression during experimental arthritis.
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影响因子：
4.4
作者：
Linsen SE;de Wit E;de Bruijn E;Cuppen E
通讯作者：
Cuppen E
影响因子：
15.8
作者：
Hultqvist M;Olofsson P;Gelderman KA;Holmberg J;Holmdahl R
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影响因子：
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作者：
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Boriek, Aladin M.
影响因子：
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作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ