Assessment on the lung injury of mice posed by airborne PM2.5 collected from developing area in China and associated molecular mechanisms: from histopathology to integrated transcriptome analysis

Abstract

Background & aimsSome epidemiological investigations have revealed airborne fine particulate matter (PM2.5) could induce adverse effects on respiratory system of human. However, the experimental evidences of the harmful effect of PM2.5 from mid-scale city in China and associated molecular mechanisms was still scarce. In this study, we aimed to evaluate the adverse effect on the lung system of PM2.5 collected from mid-city of China and elucidate the underlying molecular mechanism through mRNA-seq and microRNA-seq integrated analysis.MethodsWe exposed male Balb/C mice to PM2.5 collected from Baoji city, China for 8 weeks (298.52 ± 25.86 μg/m3) using a whole-body exposure system. Micro-CT and histopathological analyses were performed to determine the morphology and histopathology changes of lung tissues induced by PM2.5. Transcriptome (both mRNA and microRNA) sequencing and the immunohistochemistry assay were performed to reveal the associated underlying mechanisms. The contents of PAHs absorbed in the PM2.5, as well as the pearson correlation index between it and the target genes and microRNA were examined.ResultsObvious lung injury including pulmonary dysfunction, immunological responses, and fibrosis were observed from the PM2.5 exposure group. The content of leucocyte of lung tissue was significantly increased. PM2.5 mainly induced immune pathways including B cell receptor signaling and cell adhesion molecules (CAMs). The expression levels of the associated genes and microRNA were verified using RT-qPCR. The protein expression of CD19, CD81, and PIK3CD involved into B cell receptor signaling significantly increased in exposure group. The concentrations of benzo(a)pyrene (BaP) showed a marked correlationship with the genes and microRNA. ConclusionsPM2.5 from the mid-scale city of China caused adverse effects on lung system of mice, which was much stronger than the mega city, indicating the health risk of the air pollution in the developing area should be paid more attention. The toxicity of PM2.5 may associated with immune system response. This work for the first time provided a new sight into the molecular mechanism of PM2.5 toxicity on lung system using transcriptomics integrated analysis and help further to develop effective measures to prevent air pollution associated lung disease, especially in the developing area in China.