Effects of chronic PM2.5 exposure on pulmonary epithelia: Transcriptome analysis of mRNA-exosomal miRNA interactions. (November 2019)

• Record Type: Journal Article
• Authors: Xu, Zihan; Wang, Ning; Xu, Ye; Hua, Li; Zhou, Dan; Zheng, Min; Deng, Xiaobei
• Is Part Of: Toxicology letters. Volume 316(2019)
• Page Start: 49
• Page End: 59
• Publication Date: 2019-11
• Subjects: PM2.5 -- Exosome -- Pulmonary diseases -- Micro-RNA -- Bioinformatics -- In vitro toxicity; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.09.010
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: We found long-term low-dose PM2.5 exposure could enhance proliferation, migration and invasion of BEAS-2B cells. We found PM2.5 could stimulate the excretion of exosomes from BEAS-2B cells. We explored the effects of PM2.5 on gene expression and exosomal miRNA expression profiles of BEAS-2B cells. We constructed DE-Exo-MiRs-DEGs networks which might contribute to the PM2.5 induced-invasive BEAS-2B phenotype. Abstract: Epidemiological studies have established the correlations between PM2.5 and a wide variety of pulmonary diseases. However, their underlying pathogeneses have not been clearly elucidated yet. In the present study, the epithelial-mesenchymal transition (EMT) phenotype with enhanced proliferation and migration activity of human pulmonary epithelial cell line BEAS-2B was observed after exposure to low dose PM2.5 exposure (50 μg/ml) for 30 passages. Then, epithelial cells derived-exosomal micro-RNA (miRNA) and intracellular total RNA were extracted, and the differentially expressed exosomal miRNAs (DE-Exo-MiRs) as well as differentially expressed protein coding genes (DEGs) were identified by RNA sequencing (RNA-seq) and transcriptome analysis. We found that chronic PM2.5 exposure stimulated the release of pulmonary epithelium derived exosomes. 45 DE-Exo-MiRs including 32 novelly predicted miRNAs and 843 DEGs between PM2.5 exposed group and the normal control were detected. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in extracellular matrix organization, focal adhesion and cancer related terms. Besides, the enrichment analyses on 7774 mRNA targets of 27 DE-Exo-MiRs predicted by MiRanda software also revealed the potential regulatory role of exosomal miRNAs in pathways in cancer, Wingless/Integrated (Wnt) signaling pathway, focal adhesion related genes and other multiple pathogenic pathways. Moreover, the interactive exosomal miRNA-mRNA pair networks were constructed using Cytoscape software. Our results provided a novel basis for a better understanding of the mechanisms of chronic PM2.5 exposure induced pulmonary disorders including pulmonary fibrosis and cancer, in which exosomal miRNAs (Exo-MiRs) potentially functions by dynamically regulating gene expressions.