Transcriptomic analysis of key genes and pathways in human bronchial epithelial cells BEAS-2B exposed to urban particulate matter.

Mengchan Zhu, Jian Wang, Cuicui Chen, Yuanlin Song, Jue Pan

Environmental science and pollution research international 2021 Feb

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Urban particulate matter (PM), a great danger to public health, is associated with increasing risk of pulmonary diseases. However, the involved key genes and signaling pathways mediating the cellular responses to urban PM are largely unknown. In this study, human bronchial epithelial cells BEAS-2B was exposed to Standard reference material (SRM) 1649b, followed by RNA-sequencing (RNA-seq) and a combination of different bioinformatics analysis. A total of 201 genes (111 upregulated and 90 downregulated) were identified as the differentially expressed genes (DEGs). Moreover, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) unveiled several significant genes and pathways involved in PM-induced lung toxicity. Protein-protein interaction (PPI) network was performed with the Search Tool for the Retrieval of Interacting Genes (STRING), and the hub gene modules were recognized by Molecular Complex Detection (MCODE), a plug-in of Cytoscape. Moreover, Connectivity Map (CMap) analysis found six candidate small molecular compounds to reverse PM-altered gene expression, including aminohippuric acid, captopril, cinoxacin, fasudil, pargyline, and altizide. Finally, the expressions of part vital genes related to inflammation (IL-1β, CXCL2, CXCL5, CXCL8), ferroptosis (HMOX1, GCLM), and autophagy (BECN1, MAPK1LC3B) were in accordance with the RNA-seq data, with a concentration-dependent manner. This study may be helpful in revealing the complex molecular mechanisms underlying PM-induced lung toxicity and provide some new therapeutic targets for PM-related pulmonary diseases.

Citation

Mengchan Zhu, Jian Wang, Cuicui Chen, Yuanlin Song, Jue Pan. Transcriptomic analysis of key genes and pathways in human bronchial epithelial cells BEAS-2B exposed to urban particulate matter. Environmental science and pollution research international. 2021 Feb;28(8):9598-9609