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 mu g/ 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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21777099]; Shanghai Municipal Commission of Health and Family Planning [201640197]; Changning District Health and Family Planning Commission [20164Y004]; Startup Fund for Youngman Research at Shanghai Jiao Tong University [15X100040063]; Shanghai Jiao Tong University Interdisciplinary Research Grant [YG2017QN71]; Shanghai College Student Innovation and Entrepreneurship Training Project [IAP11151]
第一作者机构：[2]Shanghai Jiao Tong Univ, Fac Publ Hlth, Sch Med, 227 South Chongqing Rd, Shanghai 200025, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, 1111 Xianxia Rd, Shanghai 200336, Peoples R China[2]Shanghai Jiao Tong Univ, Fac Publ Hlth, Sch Med, 227 South Chongqing Rd, Shanghai 200025, Peoples R China[*1]Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, No.227 South Chongqing Road, Shanghai, China.[*2]Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No.1111 Xianxia Road, Shanghai, China
推荐引用方式(GB/T 7714)：
Xu Zihan,Wang Ning,Xu Ye,et al.Effects of chronic PM2.5 exposure on pulmonary epithelia: Transcriptome analysis of mRNA-exosomal miRNA interactions[J].TOXICOLOGY LETTERS.2019,316:49-59.doi:10.1016/j.toxlet.2019.09.010.
APA：
Xu, Zihan,Wang, Ning,Xu, Ye,Hua, Li,Zhou, Dan...&Deng, Xiaobei.(2019).Effects of chronic PM2.5 exposure on pulmonary epithelia: Transcriptome analysis of mRNA-exosomal miRNA interactions.TOXICOLOGY LETTERS,316,
MLA：
Xu, Zihan,et al."Effects of chronic PM2.5 exposure on pulmonary epithelia: Transcriptome analysis of mRNA-exosomal miRNA interactions".TOXICOLOGY LETTERS 316.(2019):49-59
