miR-146a in PBMCs modulates Th1 function in patients with acute coronary syndrome
miR-146a in PBMCs modulates Th1 function in patients with acute coronary syndrome
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DOI：
10.1038/icb.2010.16
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发表时间：
2010-07-01
影响因子：
4
通讯作者：
Zeng, Qiutang
中科院分区：
文献类型：
--
作者：
Guo, Min;Mao, Xiaobo;Zeng, Qiutang
Th1细胞的上调在动脉粥样硬化(AS)的发生发展中起着重要作用。最近的研究表明，miR-146a是一种在Th1诱导的自身免疫性疾病中特异性高表达的microRNA。本研究的目的是探讨miR-146a在急性冠脉综合征(ACS)发病中的可能机制。结果表明，急性冠脉综合征患者外周血单个核细胞(PBMC)miR-146a的表达明显增加。我们发现，在PBMC中过表达miR-146a可以显著上调Th1细胞的功能。此外，我们还发现miR-146a处理可以通过转录后增强T-bet通路来调节Th1的分化。此外，本研究还提供了miR-146a体外处理可诱导AS中关键的促炎细胞因子和关键转录因子--肿瘤坏死因子-α、单核细胞趋化蛋白-1、核因子-kappa B p65蛋白表达的证据。相反，miR-146a抑制剂可以显著减弱这些现象。这些结果支持miR-146a可能是Th1分化的一个新的调节因子和AS和ACS的一个新的治疗靶点。《免疫学和细胞生物学》(2010年)885555564；doi：10.1038/icb.2010.16；2010年3月2日在线发布
The upregulation of Th1 cells has been suggested to have an essential function in the development of atherosclerosis (AS). Recent studies indicate that miR-146a is a microRNA specifically and highly expressed in Th1-driven autoimmune disease. The aim of the study was to investigate the possible mechanisms of the miR-146a in the onset of acute coronary syndrome (ACS). The results showed that the expression of miR-146a in peripheral blood mononuclear cells (PBMCs) was significantly increased in patients with ACS. We showed that overexpression of miR-146a in PBMCs could significantly upregulate the function of Th1 cells. Furthermore, we showed that miR-146a treatment could modulate the Th1 differentiation through posttranscriptional enhancing the T-bet pathway in PBMCs. In addition, this study also provided evidence that miR-146a treatment in vitro could induce the protein expression of TNF-alpha, MCP-1, NF-kappa B p65, which are key pro-inflammatory cytokines and critical transcription factor in AS. In contrast, miR-146a inhibitor could attenuate these phenomena significantly. The results support the concept that miR-146a may be a novel regulatory factor in Th1 differentiation and a new therapeutic target for AS and ACS. Immunology and Cell Biology (2010) 88, 555-564; doi:10.1038/icb.2010.16; published online 2 March 2010