Kim Hyo Jeong, Kim So Young, Kwon Jee Young, Kim Yeo Jin, Hun Kang Seung, Jang Won-Hee, Lee Jun Ho, Seo Myung-Whan, Song Jae-Jun, Seo Young Rok, Park Moo Kyun
Department of Life Science, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-820, South Korea.
Institute of Environmental Medicine, Dongguk University, Seoul, South Korea.
PLoS One. 2016 Nov 10;11(11):e0166044. doi: 10.1371/journal.pone.0166044. eCollection 2016.
Air pollutants are associated with inflammatory diseases such as otitis media (OM). Significantly higher incidence rates of OM are reported in regions with air pollution. Diesel exhaust particles (DEPs) comprise a major class of contaminants among numerous air pollutants, and they are characterized by a carbonic mixture of polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, and small amounts of sulfate, nitrate, metals and other trace elements. DEP exposure is a risk factor for inflammatory diseases. Our previous study identified potential biomarkers using gene expression microarray and pathway analyses in an in vitro system. Although in vitro investigations have been conducted to elucidate plausible biomarkers and molecular mechanisms related to DEP exposure, in vivo studies are necessary to identify the exact biological relevance regarding the incidence of OM caused by DEP exposure. In this study, we identified potential molecular biomarkers and pathways triggered by DEP exposure in a rodent model.
Transcriptomic analysis was employed to identify novel potential biomarkers in the middle ear of DEP-exposed mice.
A total of 697 genes were differentially expressed in the DEP-exposed mice; 424 genes were upregulated and 273 downregulated. In addition, signaling pathways among the differentially expressed genes mediated by DEP exposure were predicted. Several key molecular biomarkers were identified including cholinergic receptor muscarinic 1 (CHRM1), erythropoietin (EPO), son of sevenless homolog 1 (SOS1), estrogen receptor 1 (ESR1), cluster of differentiation 4 (CD4) and interferon alpha-1 (IFNA1).
Our results shed light on the related cell processes and gene signaling pathways affected by DEP exposure. The identified biomarkers might be potential candidates for determining early diagnoses and effective treatment strategies for DEP-mediated disorders.
空气污染物与诸如中耳炎（OM）等炎症性疾病相关。在空气污染地区，中耳炎的发病率显著更高。柴油废气颗粒（DEP）是众多空气污染物中的主要污染物类别，其特征是含有多环芳烃（PAH）、硝基多环芳烃的碳混合物，以及少量的硫酸盐、硝酸盐、金属和其他微量元素。接触DEP是炎症性疾病的一个风险因素。我们之前的研究在体外系统中使用基因表达微阵列和通路分析确定了潜在的生物标志物。尽管已经进行了体外研究以阐明与DEP暴露相关的合理生物标志物和分子机制，但体内研究对于确定DEP暴露导致中耳炎发病率的确切生物学相关性是必要的。在本研究中，我们在啮齿动物模型中确定了由DEP暴露触发的潜在分子生物标志物和通路。
采用转录组分析来确定暴露于DEP的小鼠中耳中的新型潜在生物标志物。
在暴露于DEP的小鼠中共有697个基因差异表达；424个基因上调，273个基因下调。此外，预测了由DEP暴露介导的差异表达基因之间的信号通路。确定了几个关键的分子生物标志物，包括毒蕈碱型胆碱能受体1（CHRM1）、促红细胞生成素（EPO）、七号染色体失活蛋白同源物1（SOS1）、雌激素受体1（ESR1）、分化簇4（CD4）和干扰素α-1（IFNA1）。
我们的结果揭示了受DEP暴露影响的相关细胞过程和基因信号通路。所确定的生物标志物可能是用于确定DEP介导疾病的早期诊断和有效治疗策略的潜在候选物。
