Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways.
Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways.
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DOI：
10.1289/ehp.0900756
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发表时间：
2009-11
影响因子：
10.4
通讯作者：
Diaz-Sanchez D
中科院分区：
文献类型：
--
作者：
Jardim MJ;Fry RC;Jaspers I;Dailey L;Diaz-Sanchez D
颗粒物（PM）与不良气道健康影响有关;然而，疾病发生的潜在机制在很大程度上仍然未知。最近，microRNAs（miRNAs;小的非编码RNA）在通过调节基因表达维持肺处于无病状态中是重要的。虽然许多研究已经显示了异常的miRNA表达模式，在患病与健康组织，很少有人知道环境因素是否可以诱导这种变化。我们使用柴油机尾气颗粒物（DEP），排放的空气中PM的最大来源，调查污染诱导的气道上皮细胞中miRNA表达的变化。我们假设DEP暴露可导致正常miRNA表达模式的破坏，代表DEP可介导疾病起始的合理新机制。人支气管上皮细胞在气-液界面上生长，直到它们达到粘膜纤毛分化。在用10 μg/cm 2 DEP处理细胞24小时后，我们使用微阵列谱分析和定量实时聚合酶链反应分析总RNA的miRNA表达。DEP暴露改变了人气道上皮细胞中miRNA的表达谱。具体而言，313个可检测的miRNAs中有197个（62.9%）上调或下调了1.5倍。对12种最改变的miRNAs的推定靶点的分子网络分析表明，DEP暴露与炎症反应途径和强烈的致瘤性疾病特征相关。环境污染物如DEP对miRNA表达谱的改变可以通过调节基因表达来改变细胞过程，这可能导致疾病的发病机制。
Particulate matter (PM) is associated with adverse airway health effects; however, the underlying mechanism in disease initiation is still largely unknown. Recently, microRNAs (miRNAs; small noncoding RNAs) have been suggested to be important in maintaining the lung in a disease-free state through regulation of gene expression. Although many studies have shown aberrant miRNA expression patterns in diseased versus healthy tissue, little is known regarding whether environmental agents can induce such changes. We used diesel exhaust particles (DEP), the largest source of emitted airborne PM, to investigate pollutant-induced changes in miRNA expression in airway epithelial cells. We hypothesized that DEP exposure can lead to disruption of normal miRNA expression patterns, representing a plausible novel mechanism through which DEP can mediate disease initiation. Human bronchial epithelial cells were grown at air–liquid interface until they reached mucociliary differentiation. After treating the cells with 10 μg/cm2 DEP for 24 hr, we analyzed total RNA for miRNA expression using microarray profile analysis and quantitative real-time polymerase chain reaction. DEP exposure changed the miRNA expression profile in human airway epithelial cells. Specifically, 197 of 313 detectable miRNAs (62.9%) were either up-regulated or down-regulated by 1.5-fold. Molecular network analysis of putative targets of the 12 most altered miRNAs indicated that DEP exposure is associated with inflammatory responses pathways and a strong tumorigenic disease signature. Alteration of miRNA expression profiles by environmental pollutants such as DEP can modify cellular processes by regulation of gene expression, which may lead to disease pathogenesis.
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DOI：
10.1165/rcmb.2006-0449oc
发表时间：
2007-08-01
影响因子：
6.4
作者：
Cao, Dongsun;Bromberg, Philip A.;Samet, James M.
通讯作者：
Samet, James M.
影响因子：
4.8
作者：
Izzotti, Alberto;Calin, George A.;De Flora, Silvio
通讯作者：
De Flora, Silvio
卡车行业工人的肺癌和车辆排气。
影响因子：
10.4
作者：
Garshick, Eric;Laden, Francine;Hart, Jaime E.;Rosner, Bernard;Davis, Mary E.;Eisen, Ellen A.;Smith, Thomas J.
通讯作者：
Smith, Thomas J.
DOI：
10.1152/ajplung.00204.2006
发表时间：
2007-02-01
影响因子：
4.9
作者：
Cao, Dongsun;Tal, Tamara L.;Samet, James M.
通讯作者：
Samet, James M.
DOI：
10.1523/jneurosci.3338-08.2008
发表时间：
2008-11-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Aschrafi A;Schwechter AD;Mameza MG;Natera-Naranjo O;Gioio AE;Kaplan BB
通讯作者：
Kaplan BB