Abstract:

Objective To analyze the effect of particulate matter 2.5（PM_2.5） on gene expression in human bronchial epithelial cells（BEAS-2B） using bioinformatics methods，screen differentially expressed genes（DEGs），in order to provide reference for respiratory system injury and mechanism caused by PM_2.5. Methods A dataset related to BEAS-2B cells exposed to PM_2.5（GSE158954） was retrieved from the Gene Expression Omnibus（GEO） database of the National Center for Biotechnology Information（NCBI） in the United States. The R language was used to screen the gene expression data matrix by DEGs，enrich the Gene Ontology（GO） function and analyze the Kyoto Encyclopedia of Genes and Genomes（KEGG） signal pathway. At the same time，the protein-protein interaction（PPI） network was constructed by using STRING database and Cytoscape3.8.0 software，the key hub genes were screened by MCODE plugin，and relative expression levels of DEGs were analyzed using the NCBI Gene database. Results The GSE158954 dataset included 6 samples：three controls（GSM4816385，GSM4816386，GSM4816387） and three PM_2.5-exposed BEAS-2B cell samples（GSM4816388，GSM4816389，GSM4816390）. The analysis results showed that a total of 235 DEGs were detected（P<0.05 and |log2fc|≥1 after correction）. Among them，there were 121 up-regulated genes and 114 down-regulated genes. GO analysis results showed that DEGs were significantly enriched in multiple biological processes，cell components and molecular function modules. In terms of biological processes（BP），they mainly involved processes such as chemotaxis of macrophages（AMs） and neutrophils，suggesting that they played a potential role in regulating immune cell migration；at the cell component（CC） level，they were concentrated in the plasma membrane，cytoplasm and cytosol regions，suggesting that DEGs might be involved in physiological activities related to these subcellular structures；the molecular function（MF） module showed that DEGs mainly played a protein binding function，which was closely related to their participation in many intracellular signal transduction pathways and molecular interactions. The KEGG analysis results showed that，in addition to virus related signaling channels，DEGs mainly participate in PI3K-Akt and other signaling pathways. Further screening identified 27 key genes，including PTGS2，CXCL8，CCL2，IL1B，TNFSF10，IL1A，JUN，IL-6，TLR3，TRIM21，USP18，IFIT5，MX1，EGFR，CASP1，STAT2，GBP1，SAMD9L，OAS2，PARP9，RTP4，IFI35，MX2，TRIM22，UBE2L6，SP110，and CMPK2. Most DEGs had relatively high expression levels in lung tissue. Conclusion This study reveals that PM_2.5 may mediate respiratory inflammatory responses and immune dysregulation by modulating 27 key genes（such as PTGS2 and CXCL8） and affecting signaling pathways such as PI3K-Akt. These findings provide novel insights into the mechanisms of PM_2.5-induced respiratory injury.

Key words: Particulate matter 2.5, BEAS-2B cells, Bioinformatics, Differentially expressed genes, PI3K-Akt signaling pathway, Inflammatory response, Immune regulation