Regulation of microRNA-155 in atherosclerotic inflammatory responses by targeting MAP3K10.
Regulation of microRNA-155 in atherosclerotic inflammatory responses by targeting MAP3K10.
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通过靶向 MAP3K10 调节 MicroRNA-155 在动脉粥样硬化炎症反应中的作用
DOI：
10.1371/journal.pone.0046551
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yan H
中科院分区：
文献类型：
--
作者：
Zhu J;Chen T;Yang L;Li Z;Wong MM;Zheng X;Pan X;Zhang L;Yan H
目的越来越多的证据表明，大量的microRNAs(MiRNAs)在细胞的增殖、凋亡和分化以及伴随炎症反应的各种疾病中发挥着重要作用。炎症被认为是动脉粥样硬化形成的主要因素。以前的研究提供了有希望的证据，支持miRNAs在心血管疾病中的作用。然而，关于这些小分子在动脉粥样硬化(AS)中的机制数据仍然缺乏。本研究旨在探讨miRNAs在AS中的潜在作用。方法与结果用TaqMan实时定量聚合酶链式反应检测miRNA转录酶。胸主动脉样本取自载脂蛋白E基因敲除小鼠，血浆样本取自冠心病患者。结果表明，与正常对照组相比，AS小鼠和冠心病患者的miR-155水平均显著升高。在体内和体外观察miR-155在动脉粥样硬化通路生理过程中的功能作用。这些观察表明，miR-155是负反馈环路的一部分，该环路下调炎性细胞因子的产生，并随着进展而减少。MIR-155还通过靶向丝裂原活化蛋白激酶10介导炎症反应和丝裂原活化蛋白激酶(MAPK)通路。结论miR-155参与AS的发生发展。它还可能通过靶向丝裂原活化蛋白激酶10参与炎症反应和MAPK通路的转录后调控。
Aims Accumulating evidence suggest that numerous microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and differentiation, as well as various diseases that accompany inflammatory responses. Inflammation is known to be a major contributor to atherogenesis. Previous studies provide promising evidence in support of the role of miRNAs in cardiovascular disease. However, mechanistic data on these small molecules in atherosclerosis (AS) are still missing. The present study aims to investigate the potential role of miRNAs in AS. Methods and Results The miRNA transcriptase was verified by TaqMan real-time polymerase chain reaction assay. Thoracic aorta samples were obtained from Apolipoprotein E knockout mice, and plasma samples were from coronary artery disease (CAD) patients. The results showed that the miR-155 level was the most significantly elevated both in AS mice and CAD patients relative to the normal control. The functional role of miR-155 in the atherosclerotic path physiological process was also observed in vivo and in vitro. The observations suggested that miR-155 is a part of a negative feedback loop, which down-modulates inflammatory cytokine production and decreases AS progression. miR-155 was also found to mediate the inflammatory response and mitogen-activated protein kinase (MAPK) pathway by targeting mitogen-activated protein kinase kinase kinase 10. Conclusions miR-155 contributes to the prevention of AS development and progression. It may also be involved in the posttranscriptional regulation of the inflammatory response and MAPK pathway by targeting mitogen-activated protein kinase kinase kinase 10.
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