Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China.
University/BHF Centre for Cardiovascular Science, Queens Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
Sci Total Environ. 2017 May 15;586:666-674. doi: 10.1016/j.scitotenv.2017.02.042. Epub 2017 Feb 16.
PM is a major public health concern and some severe diseases have been attributed to exposure to PM. However, a comprehensive understanding of gene and microRNA expression patterns induced by PM is missing. The objective of this study was to evaluate the toxicity of PM via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process. Pathway and Signal-net analysis showed that the critical pathway involved in the response to exposure to PM was the metabolism of xenobiotics by cytochrome P450. Results from verification experiments also demonstrated that the key genes with degree higher than 10 induced by PM were related to metabolism of xenobiotics by cytochrome P450, including cyp3a65, mgst2, gstp1, gsto2, gsto1, cyp1a, ehx1, gstal and aldh3b1. The differential expression of 8 microRNAs corresponding to those in the human genome, revealed that PM could up-regulate let-7b, miR-153b-3p, miR-122, miR-24 and down-regulate let-7i, miR-19a-3p, miR-19b-3p and miR-7a, which suggested PM had multiple means through which it induced toxicity in living organisms, such as suppression of adaptive immune responses, autophagy, deregulation of metabolism, impaired vasorelaxation, progression of cancers, as well as hypertension, atherosclerosis and myocardial infarction.
PM 是一个主要的公共卫生关注点，一些严重的疾病已经归因于 PM 的暴露。然而，对于 PM 诱导的基因和 microRNA 表达模式的综合理解仍然缺乏。本研究的目的是通过全基因组转录分析评估 PM 在模式硬骨鱼斑马鱼（Danio rerio）中的毒性。基因本体论分析表明，PM 诱导的影响最大的基因功能类别包括氧化还原过程、运输、对外源化学物质刺激的反应、对化学刺激的反应和代谢过程。途径和信号网络分析表明，暴露于 PM 中涉及的关键途径是细胞色素 P450 对外源化学物质的代谢。验证实验的结果也表明，PM 诱导的关键基因的度值高于 10，与细胞色素 P450 对外源化学物质的代谢有关，包括 cyp3a65、mgst2、gstp1、gsto2、gsto1、cyp1a、ehx1、gstal 和 aldh3b1。与人类基因组对应的 8 个 microRNA 的差异表达表明，PM 可以上调 let-7b、miR-153b-3p、miR-122、miR-24，下调 let-7i、miR-19a-3p、miR-19b-3p 和 miR-7a，这表明 PM 有多种诱导生物体毒性的途径，如抑制适应性免疫反应、自噬、代谢失调、血管舒张受损、癌症进展以及高血压、动脉粥样硬化和心肌梗死。
