School of Public Health, Shanghai Institute of Infectious Disease and Biosecurity, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China.
Department of Systems Biology for Medicine, and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Environ Int. 2022 Sep;167:107430. doi: 10.1016/j.envint.2022.107430. Epub 2022 Jul 26.
The underlying mechanisms for health effects of traffic-related air pollution (TRAP) are still unclear. Small RNA sequencing (RNA-seq) in exosomes represents as a powerful approach to elucidate biological pathways in response to environmental exposure. We therefore aimed to explore impact of TRAP exposure on exosomal miRNAs.
We performed a randomized, crossover study among 35 healthy college students in Shanghai, China. Participants were randomly assigned to 4-hour exposure in a traffic-polluted Road and in a traffic-free Park, respectively, intermitted by a washout period (at least 2 weeks). RNA-seq was conducted to identify plasma-derived exosomal miRNAs and the differential miRNAs were explored using linear mixed-effect models. Pathway enrichment was conducted using ingenuity pathway analysis. Further, we validated several selected miRNAs by droplet digital PCR (ddPCR).
The average concentrations of air pollutants including ultrafine particles, black carbon, nitrogen dioxide, and carbon dioxide were 2-3 times higher in the Road compared to those in the Park. We identified 271 exosomal miRNAs (212 up-regulated and 59 down-regulated) that were significantly associated with TRAP. We found 5 miRNAs with 242 experimentally validated mRNA targets that were involved in cardiovascular pathway, cytokine signaling, and immune response. The ddPCR analysis suggested that miR-3612, miR-21-5p, and miR-195-5p were significantly changed following TRAP exposure.
For the first time this trial characterized the genome-wide changes of exosomal miRNA associated with TRAP exposure. The molecular profiling of exosomal miRNAs and "novel" associations of some miRNAs were useful for understanding on biological mechanisms for the adverse effects of TRAP.
交通相关空气污染（TRAP）对健康影响的潜在机制仍不清楚。外泌体中的小 RNA 测序（RNA-seq）代表了一种阐明环境暴露反应中生物学途径的有力方法。因此，我们旨在探讨 TRAP 暴露对外泌体 miRNAs 的影响。
我们在中国上海的 35 名健康大学生中进行了一项随机、交叉研究。参与者被随机分配到交通污染的道路和交通免费的公园进行 4 小时暴露，间隔一个洗脱期（至少 2 周）。进行 RNA-seq 以鉴定血浆衍生的外泌体 miRNAs，并用线性混合效应模型探索差异 miRNAs。采用 ingenuity pathway analysis 进行途径富集。此外，我们通过数字 PCR（ddPCR）验证了几个选定的 miRNA。
道路空气中的空气污染物（包括超细颗粒、黑碳、二氧化氮和二氧化碳）的平均浓度比公园高出 2-3 倍。我们鉴定出 271 个与 TRAP 显著相关的外泌体 miRNAs（212 个上调和 59 个下调）。我们发现了 5 个 miRNA，它们有 242 个经过实验验证的 mRNA 靶标，涉及心血管途径、细胞因子信号和免疫反应。ddPCR 分析表明，miR-3612、miR-21-5p 和 miR-195-5p 在 TRAP 暴露后明显改变。
这是首次对与 TRAP 暴露相关的外泌体 miRNA 的全基因组变化进行了描述。外泌体 miRNA 的分子谱分析和一些 miRNA 的“新”关联有助于理解 TRAP 不良影响的生物学机制。
