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首页> 外文期刊>Journal of applied toxicology >Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells
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Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells

机译：在健康工人和A549细胞中，在颗粒物质暴露时改变微肠池相关的microRNA表达

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Cardiovascular disease risk has been consistently linked with particulate matter (PM) exposure. Cell-derived microvesicles (MVs) are released into plasma and transfer microRNAs (miRNAs) between tissues. MVs can be produced by the respiratory system in response to proinflammatory triggers, enter the circulatory system and remotely modify gene expression in cardiovascular tissues. However, whether PM affects MV signaling has never been investigated. In this study, we evaluated expression of microRNAs contained within plasma MVs upon PM exposure both in vivo and in vitro. In the in vivo study, we isolated plasma MVs from healthy steel plant workers before and after workplace PM exposure. We measured the expression of 88 MV-associated miRNAs by real-time polymerase chain reaction. To assess a possible source of the MV miRNAs identified in vivo, we measured their miRNA expression in PM-treated A549 pulmonary cell lines in vitro. MiRNA profiling of plasma MVs showed 5.62- and 13.95-fold increased expression of miR-128 and miR-302c, respectively, after 3 days of workplace PM exposure (P<0.001). According to Ingenuity Pathway Analysis, miR-128 is part of coronary artery disease pathways, and miR-302c is part of coronary artery disease, cardiac hypertrophy and heart failure pathways. In vitro experiments confirmed a dose-dependent expression of miR-128 in MVs released from A549 cells after 6h of PM treatment (P=0.030). MiR-302c was expressed neither from A549 cells nor in reference lung RNA. These results suggest novel PM-activated molecular mechanisms that may mediate the effects of air pollution and could lead to the identification of new diagnostic and therapeutic interventions. Copyright (c) 2014 The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd.
机译：心血管疾病风险与颗粒物质（PM）暴露一致。将细胞衍生的微泡（MV）释放到组织之间的血浆中并转移微小RNA（miRNA）。 MV可以通过呼吸系统来产生响应于促炎触发器，进入循环系统并远程修饰心血管组织中的基因表达。但是，PM是否影响MV信令从未被调查过。在该研究中，我们在体内和体外曝光时评估了PM曝光的血浆MV中含有的MicroRNA的表达。在体内研究中，我们在下班PM暴露之前和之后的健康钢铁厂工人的血浆MV。我们通过实时聚合酶链反应测量了88个MV相关的miRNA的表达。为了评估体内鉴定的MV miRNA的可能来源，我们在体外测量了它们在PM处理的A549肺细胞系中的miRNA表达。血浆MVs的miRNA分析分别在工作场所PM暴露3天后分别增加了5.62-13.95倍，分别增加了miR-128和miR-302c的表达（P <0.001）。根据Ingenuity途径分析，MiR-128是冠状动脉疾病途径的一部分，MiR-302C是冠状动脉疾病，心肺肥大和心力衰竭途径的一部分。体外实验证实了在PM处理6小时后从A549细胞释放的MiR-128中miR-128的剂量依赖性表达（P = 0.030）。 MIR-302C既不从A549细胞表达，也不表达参考肺RNA。这些结果表明了新型PM激活的分子机制，可能介导空气污染的影响，并可能导致鉴定新的诊断和治疗干预措施。版权所有（c）2014作者。 John Wiley＆Sons Ltd.出版的应用毒理学杂志CHINESE

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