Assessment on the lung injury of mice posed by airborne PMcollected from developing area in China and associated molecular mechanisms by integrated analysis of mRNA-seq and miRNA-seq.
Ecotoxicol Environ Saf. 2021 Aug 17 ;224:112661. Epub 2021 Aug 17. PMID: 34416640
Some epidemiological evidences showed exposure of airborne fine particulate matter (PM) was associated with lung dysfunction. However, the adverse effects of PMfrom 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 PMcollected from mid-scale city (Baoji), China for 8 weeks (mean concentration 298.52 ± 25.86 μg/mat 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/min the exposure chamber, respectively. Obvious lung injury including pulmonary inflammation and fibrosis (p < 0.05 compared with the control) were found from PMexposure group determined by micro-CT and histopathological assays, respectively, suggesting the health risk posed by PMfrom 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 PMdocumented 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 PMilluminated using interactive analysis (p < 0.05). This work for the first time showed the adverse effects of PMin 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.