The effect of exposure time and concentration of airborne PM2.5 on lung injury in mice: A transcriptome analysis
The effect of exposure time and concentration of airborne PM2.5 on lung injury in mice: A transcriptome analysis
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空气中 PM2.5 的暴露时间和浓度对小鼠肺损伤的影响：转录组分析
DOI：
10.1016/j.redox.2019.101264
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发表时间：
2019-09-01
期刊：
影响因子：
11.4
通讯作者：
Lu, Zhongbing
中科院分区：
文献类型：
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作者：
Wang, Hongyun;Shen, Xiyue;Lu, Zhongbing
流行病学研究已经很好地证明了空气中细颗粒物(PM2.5)浓度与呼吸道疾病风险之间的联系。然而，PM2.5有害影响的潜在机制尚未完全了解。在本研究中，我们通过全身暴露系统将C57BL/6J小鼠暴露于空气中的PM2.5 3个月(日均浓度接近50或类似于110微克/米(3)，定义为PM2.5-3L或PM2.5-3H)或6个月(日均浓度类似于50微克/米(3)，定义为PM2.5-6L)。组织学和生化分析显示，PM2.5-3H暴露引起的肺损伤比PM2.5-3L暴露更严重，且差异大于PM2.5-6L暴露与PM2.5-3L暴露。利用RNA测序技术，我们发现暴露于不同浓度PM2.5的肺组织具有不同的转录水平。与PM2.5-3L或PM2.5-6L相比，PM2.5-3H暴露引起的肺组织差异表达基因(DEG)更多。PM2.5-3L和PM2.5-6L暴露诱导的DEGS主要集中在免疫通路，包括造血细胞谱系和细胞因子-细胞因子受体相互作用，而PM2.5-3H暴露诱导的DEGS主要富集于心血管疾病通路，包括肥厚型心肌病和扩张型心肌病。此外，我们还发现CD51的上调以及Hspa1和Peroxiredosin-4的减少与PM2.5诱导的肺部炎症和氧化应激有关。这些结果可能为了解PM2.5的细胞毒性机制提供新的见解，并有助于开发新的策略来减轻空气污染相关的呼吸道疾病。
The association between airborne fine particulate matter (PM2.5) concentration and the risk of respiratory diseases has been well documented by epidemiological studies. However, the mechanism underlying the harmful effect of PM2.5 has not been fully understood. In this study, we exposed the C57BL/6J mice to airborne PM2.5 for 3 months (mean daily concentration similar to 50 or similar to 110 mu g/m(3), defined as PM2.5-3L or PM2.5-3H) or 6 months (mean daily concentration similar to 50 mu g/m(3), defined as PM2.5-6L) through a whole-body exposure system. Histological and biochemical analysis revealed that PM2.5-3H exposure caused more severe lung injury than did PM2.5-3L, and the difference was greater than that of PM2.5-6L vs PM2.5-3L exposure. With RNA-sequencing technique, we found that the lungs exposed with different concentration of PM2.5 have distinct transcriptional profiles. PM2.5-3H exposure caused more differentially expressed genes (DEGs) in lungs than did PM2.5-3L or PM2.5-6L. The DEGs induced by PM2.5-3L or PM2.5-6L exposure were mainly enriched in immune pathways, including Hematopoietic cell lineage and Cytokine-cytokine receptor interaction, while the DEGs induced by PM2.5-3H exposure were mainly enriched in cardiovascular disease pathways, including Hypertrophic cardiomyopathy and Dilated cardiomyopathy. In addition, we found that upregulation of Cd5l and reduction of Hspa1 and peroxiredoxin-4 was associated with PM2.5-induced pulmonary inflammation and oxidative stress. These results may provide new insight into the cytotoxicity mechanism of PM2.5 and help to development of new strategies to attenuate air pollution associated respiratory disease.