Project description:Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (< 2.5 µm) PM (PM2.5). Although some of these changes have been reported in other studies, a comparison of how different doses and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. We exposed BEAS-2B, a bronchial epithelial cell line, to a single exposure of high (30 µg/cm2) or low (1 µg/cm2) dose of PM2.5 (obtained from Beijing, China in 2015) for 24 hours. We also exposed BEAS-2B cells to repeated exposures of low dose (1 µg/cm2) PM2.5 every day for seven days. We then examined the transcriptomic changes (by RNA-Seq) and DNA methylomic changes (by enhanced reduced representation bisulfite sequencing). Widespread changes in gene expression occurred after cells were exposed to a single, high dose (30 µg/cm2) exposure of PM2.5 for 24 h. These genes were enriched in pathways regulating MAPK signaling, PI3K-Akt signaling, cytokine interactions, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes. Cells exposed to a lower dose (1 µg/cm2) of PM2.5 demonstrated a similar, but more attenuated change in gene expression. Cells exposed to repeated doses of PM2.5 for seven days, however, demonstrated a different set of genes that were differentially expressed compared to a single exposure. The DNA methylation changes that occurred with repeated, low dose exposure were also different from single high dose exposures and skewed towards overall hypomethylation. This hypomethylation corresponded with an increase in expression of ten-eleven translocation enzymes. Overall, these data demonstrate how variations in dose and duration of PM2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells.

Project description:PM2.5 can harm various systems in the human body. However, due to the limitations of epidemiology and toxicology, the disease types, shared and specific pathogenic mechanisms induced by PM2.5 in various human systems are not comprehensive and in-depth revealed. Thus, this study conducted an analysis on the aforementioned issues in respiratory, circulatory, endocrine, female, and male urogenital systems. According to this study, PM2.5 was more likely to induce pulmonary emphysema, reperfusion injury, malignant neoplasm of thyroid, endometriosis of ovary, nephritis in above each system respectively. FOS, extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis was the most important co-existing gene, cellular component, biological process, molecular function, and pathway in five systems targeted by PM2.5. Furthermore, BTG2, BIRC5, NFE2L2, TBK1, and STAT1 were significantly uniquely targeted by PM2.5 in each system respectively. Important disease related cellular component, biological process, and molecular function were highly specially induced by PM2.5, such as response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon were the top 1 uq-existing biological processes in each system respectively. PM2.5 highly specially acted on the key disease related pathway, such as PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female), and neuroactive ligand-receptor interaction (male). This study provides a new analysis method to clarify PM2.5-related disease types, which is an important supplement to epidemiological investigation. Furthermore, this study has clarified the risks of PM2.5 exposure, elucidated the pathogenic mechanisms, and provided scientific support for promoting precise prevention and treatment of PM2.5-related diseases.

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The effect of exposure to PM2.5 from the cowshed environment on the ovaries of rats

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