Dai Shuiping, Wang Zhenglu, Yang Ying, Guo Tingting, Li Weimin
National Center for Geriatrics Clinical Medicine Research, Department of Geriatrics and Gerontology, West China Hospital, Sichuan University, Chengdu 610041, China.
College of oceanography, Hohai University, Nanjing 210098, China.
Ecotoxicol Environ Saf. 2021 Nov;224:112661. doi: 10.1016/j.ecoenv.2021.112661. Epub 2021 Aug 17.
Some epidemiological evidences showed exposure of airborne fine particulate matter (PM) was associated with lung dysfunction. However, the adverse effects of PM from mid-scale city of China on the respiratory system were unknown. Correspondingly, the mechanisms, especially the epigenetic mechanism regulated by miRNAs, involved in PM-induced lung injury has not been fully understood. In this study, male Balb/C mice were exposed to PM collected from mid-scale city (Baoji), China for 8 weeks (mean concentration 298.52 ± 25.86 μg/m at exposure chamber) using a whole-body exposure system. The carbon component was the main ingredient (45.80%) of PM2.5 followed by ions (43.19%). Meanwhile, the sum concentrations of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes (C18-C33) were 570.48 and 2029.13 ng/m in the exposure chamber, respectively. Obvious lung injury including pulmonary inflammation and fibrosis (p < 0.05 compared with the control) were found from PM exposure group determined by micro-CT and histopathological assays, respectively, suggesting the health risk posed by PM from mid-scale city of China should be concerned. The integrated analysis between mRNA-seq and miRNA-seq revealed the differentially expression genes in lung tissues were enriched in immune pathways including B cell receptor signaling (p = 0.078) and cell adhesion molecules (CAMs) (p = 0.0068). The expression profiles of the genes and corresponding mRNAs involved into the immune pathways determined by RT-qPCR analysis were consistent with them conducted by transcriptome. Moreover, the expression levels of the proteins (i.e., CD19, CD81, PIK3CD, and CD22) involved into B cell receptor signaling pathway from exposure group were 1.71- to 6.948- folds compared with the control, validating the results of the genes expression profiles. Further, canonical correlation analysis (CCA) and multiple correlation analysis between the target genes and components of PM documented the organic compounds (i.e., Benzo(a)pyrene (p = 0.012) and octadecane (p = 0.05)) and inorganic elements (i.e., Cl, Ti, Al, and Zn) was the key environmental factors. Cd19, Pik3cd, and Cd8b1 might be the key genes for lung dysfunction induced by PM illuminated using interactive analysis (p < 0.05). This work for the first time showed the adverse effects of PM in mid-scale city in China on respiratory system should be concerned, and the associated epigenetic mechanism regulated by miRNA were revealed. These results may provide new insight into the development of future assessment on the air pollution associated respiratory disease.
一些流行病学证据表明，暴露于空气中的细颗粒物（PM）与肺功能障碍有关。然而，中国中型城市的PM对呼吸系统的不良影响尚不清楚。相应地，PM诱导肺损伤所涉及的机制，尤其是由miRNA调控的表观遗传机制，尚未完全明确。在本研究中，雄性Balb/C小鼠使用全身暴露系统，暴露于从中国中型城市（宝鸡）采集的PM中8周（暴露舱内平均浓度为298.52±25.86μg/m）。碳成分是PM2.5的主要成分（45.80%），其次是离子（43.19%）。同时，暴露舱内多环芳烃（PAHs）和正构烷烃（C18 - C33）的总浓度分别为570.48和2029.13 ng/m。分别通过微CT和组织病理学分析发现，PM暴露组存在明显的肺损伤，包括肺部炎症和纤维化（与对照组相比，p < 0.05），这表明中国中型城市的PM所带来的健康风险应受到关注。mRNA - seq和miRNA - seq的综合分析显示，肺组织中差异表达基因富集于免疫途径，包括B细胞受体信号通路（p = 0.078）和细胞粘附分子（CAMs）（p = 0.0068）。通过RT - qPCR分析确定的参与免疫途径的基因和相应mRNA的表达谱与转录组分析结果一致。此外，暴露组中参与B细胞受体信号通路的蛋白质（即CD19、CD81、PIK3CD和CD22）的表达水平与对照组相比为1.71至6.948倍，验证了基因表达谱的结果。进一步地，目标基因与PM成分之间的典型相关分析（CCA）和多重相关分析表明，有机化合物（即苯并(a)芘（p = 0.012）和十八烷（p = 0.05））以及无机元素（即Cl、Ti、Al和Zn）是关键环境因素。使用交互分析表明，Cd19、Pik3cd和Cd8b1可能是PM诱导肺功能障碍的关键基因（p < 0.05）。这项工作首次表明，中国中型城市的PM对呼吸系统的不良影响应受到关注，并揭示了由miRNA调控的相关表观遗传机制。这些结果可能为未来空气污染相关呼吸道疾病评估的发展提供新的见解。
