Bollati Valentina, Marinelli Barbara, Apostoli Pietro, Bonzini Matteo, Nordio Francesco, Hoxha Mirjam, Pegoraro Valeria, Motta Valeria, Tarantini Letizia, Cantone Laura, Schwartz Joel, Bertazzi Pier Alberto, Baccarelli Andrea
Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Center of Molecular and Genetic Epidemiology, Milan, Italy.
Environ Health Perspect. 2010 Jun;118(6):763-8. doi: 10.1289/ehp.0901300. Epub 2010 Jan 8.
Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate the expression of broad gene networks at the posttranscriptional level.
We evaluated the effects of exposure to PM and PM metal components on candidate miRNAs (miR-222, miR-21, and miR-146a) related with oxidative stress and inflammatory processes in 63 workers at an electric-furnace steel plant.
We measured miR-222, miR-21, and miR-146a expression in blood leukocyte RNA on the first day of a workweek (baseline) and after 3 days of work (postexposure). Relative expression of miRNAs was measured by real-time polymerase chain reaction. We measured blood oxidative stress (8-hydroxyguanine) and estimated individual exposures to PM1 (< 1 microm in aerodynamic diameter), PM10 (< 10 microm in aerodynamic diameter), coarse PM (PM10 minus PM1), and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and postexposure measurements.
Expression of miR-222 and miR-21 (using the 2-DeltaDeltaCT method) was significantly increased in postexposure samples (miR-222: baseline = 0.68 +/- 3.41, postexposure = 2.16 +/- 2.25, p = 0.002; miR-21: baseline = 4.10 +/- 3.04, postexposure = 4.66 +/- 2.63, p = 0.05). In postexposure samples, miR-222 expression was positively correlated with lead exposure (beta = 0.41, p = 0.02), whereas miR-21 expression was associated with blood 8-hydroxyguanine (beta = 0.11, p = 0.03) but not with individual PM size fractions or metal components. Postexposure expression of miR-146a was not significantly different from baseline (baseline = 0.61 +/- 2.42, postexposure = 1.90 +/- 3.94, p = 0.19) but was negatively correlated with exposure to lead (beta = -0.51, p = 0.011) and cadmium (beta = -0.42, p = 0.04).
Changes in miRNA expression may represent a novel mechanism mediating responses to PM and its metal components.
基因表达模式的改变介导了颗粒物（PM）对人类健康的影响，但PM改变基因表达的机制在很大程度上尚未明确。微小RNA（miRNA）是高度保守的非编码小RNA，在转录后水平调节广泛的基因网络表达。
我们评估了在一家电炉钢厂工作的63名工人暴露于PM及其金属成分对与氧化应激和炎症过程相关的候选miRNA（miR-222、miR-21和miR-146a）的影响。
我们在工作周的第一天（基线）和工作3天后（暴露后）测量了血液白细胞RNA中miR-222、miR-21和miR-146a的表达。通过实时聚合酶链反应测量miRNA的相对表达。我们测量了血液氧化应激（8-羟基鸟嘌呤），并估计了基线和暴露后测量之间个体对PM1（空气动力学直径<1微米）、PM10（空气动力学直径<10微米）、粗颗粒物（PM10减去PM1）和PM金属成分（铬、铅、镉、砷、镍、锰）的暴露情况。
暴露后样本中miR-222和miR-21的表达（使用2-ΔΔCT法）显著增加（miR-222：基线=0.68±3.41，暴露后=2.16±2.25，p = 0.002；miR-21：基线=4.10±3.04，暴露后=4.66±2.63，p = 0.05）。在暴露后样本中，miR-222表达与铅暴露呈正相关（β = 0.41，p = 0.02），而miR-21表达与血液8-羟基鸟嘌呤相关（β = 0.11，p = 0.03），但与个体PM粒径分级或金属成分无关。miR-146a暴露后表达与基线无显著差异（基线=0.61±2.42，暴露后=1.90±3.94，p = 0.19），但与铅暴露（β = -0.51，p = 0.011）和镉暴露（β = -0.42，p = 0.04）呈负相关。
miRNA表达的变化可能代表了一种介导对PM及其金属成分反应的新机制。
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