Zhou Tianyu, Yu Qing, Sun Chao, Wang Yunxia, Zhong Yijue, Wang Guangfa
Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing100034, China.
J Thorac Dis. 2018 Dec;10(12):7073-7080. doi: 10.21037/jtd.2018.12.42.
Fine particulate exposure (PM) is a risk factor of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), but the mechanism underlying was not clear. Recent studies found blood microRNAs (miRNAs) are potential indicators of either COPD or PM exposure, but these results had no unified conclusions. We suggested it was more targeted to find disease related miRNAs first and then observe them during PM exposure. Firstly, in order to screen COPD associated miRNAs, we identified differentially expressed blood miRNAs contrasting COPD participants (n=6) without diagnose of COPD or related treatment before and matched control (n=6). In total, 21 miRNAs were differentially expressed in COPD individuals and expression of miR-495-3p, miR-223-5p and miR-194-3p were further validated using qRT-PCR. The results showed miR-495-3p and miR-223-5p significantly increased whereas miR-194-3p decreased marginally (P=0.058) in COPD participants. Secondly, in order to recognize the relevance between these miRNAs and PM exposure, we designed an independent time-series study nested within "low-high-low" pollution levels. The expression of blood miR-495-3p, miR-223-5p and miR-194-3p were detected before and after exposure (n=8). The results showed expression of miR-223-5p increased significantly while expression of miR-194-3p decreased significantly after exposure. The Pearson analysis showed only miR-194-3p showed a positive statistically correlation with lag0-1 forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) during exposure of PM. So miR-194-3p might be a potential regulator in the toxicological pathways of both PM exposure and COPD. As this was a pilot study, formal and large-scale studies should be planned in the future.
细颗粒物暴露(PM)是慢性阻塞性肺疾病(COPD)等肺部疾病的一个风险因素,但其潜在机制尚不清楚。最近的研究发现血液中的微小RNA(miRNA)是COPD或PM暴露的潜在指标,但这些结果尚无统一结论。我们建议更有针对性地先找到与疾病相关的miRNA,然后在PM暴露期间对其进行观察。首先,为了筛选与COPD相关的miRNA,我们对比了6名未被诊断为COPD或未接受相关治疗的COPD参与者及匹配的对照组(6名),鉴定出差异表达的血液miRNA。总共21种miRNA在COPD个体中差异表达,其中miR-495-3p、miR-223-5p和miR-194-3p的表达通过qRT-PCR进一步验证。结果显示,COPD参与者中miR-495-3p和miR-223-5p显著增加,而miR-194-3p略有下降(P = 0.058)。其次,为了认识这些miRNA与PM暴露之间的相关性,我们设计了一项嵌套在“低-高-低”污染水平内的独立时间序列研究。在暴露前后检测了血液中miR-495-3p、miR-223-5p和miR-194-3p的表达(n = 8)。结果显示,暴露后miR-223-5p的表达显著增加,而miR-194-3p的表达显著下降。Pearson分析显示,在PM暴露期间,只有miR-194-3p与滞后0-1秒用力呼气量(FEV1)和用力肺活量(FVC)呈正相关。因此,miR-194-3p可能是PM暴露和COPD毒理学途径中的一个潜在调节因子。由于这是一项初步研究,未来应计划进行正式的大规模研究。