二氧化硅暴露对呼吸道上皮细胞基因表达的影响

doi:10.3969/j.issn.1004-616x.2024.04.004

Abstract

Abstract: OBJECTIVE：Bioinformatics method was used to explore changes of gene expression in NHBE cells exposed to SiO₂ and key genes were verified by experiments，to provide information for enhanced diagnosis and treatment of silicosis. METHODS：GSE62769，a dataset related to silica，was obtained from GEO database. The differentially expressed genes (DEGs)，GO functional enrichment analysis and KEGG signal pathway analysis were carried out with R language 3.6.3. At the same time，the protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape software，and key genes were screened by MCODE plug-in. Finally，A549 cells were exposed to 0，50，100，200 μg/mL SiO₂ for 24 h and the bioinformatics analysis results of key gene expression levels were extensively verified by RT-qPCR method. RESULTS：A total of 48 DEGs were screened. The results of GO and KEGG analysis showed that DEGs were mainly involved in biological processes such as lipopolysaccharide reaction and reaction to bacterial molecules，etc.，and signal pathways such as cytokine-cytokine receptor interaction，etc. Eleven key genes of PPI network were selected by MCODE plug-in，which were CXCL8，CXCL10，TLR2，JUN，ICAM1，CXCL1，MMP1，TNFAIP3，CCL20，CXCL2 and CXCL3.Results from RT-qPCR analyses showed that expressions of CXCL8，JUN，ICAM1，CXCL1，MMP1，TNFAIP3，CCL20 and CXCL3 were significantly up-regulated in the A549 cells treated with 200 μg/mL SiO₂ suspension，which was consistent with the trend of gene expression on NHBE cells in bioinformatics analysis. CONCLUSION：Based on bioinformatics and experimental verification methods，11 key DEG related to SiO₂ exposed respiratory epithelial cells were screened. Our results provided new information on pathogenesis of silicosis，and identified several possible targets for the early diagnosis and treatment of silicosis.

Key words: silicosis, epithelial cells, silica, bioinformatics, differentially expressed genes

CLC Number:

R135.2

WU Mengyu, DE Xiaoming, SHAN Jing, LI Jie, ZHANG Yingchi, XU Haiming. Effect of silica exposure on gene expression in respiratory epithelium[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(4): 268-274,280.

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Effect of silica exposure on gene expression in respiratory epithelium

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