Profiling of the silica‐induced molecular events in lung epithelial cells using the RNA‐Seq approach

• Published in: Journal of applied toxicology 2017-10, Vol.37 (10), p.1162-1173
• Main Authors: Chan, Judy Y. W., Tsui, Joseph C. C., Law, Patrick T. W., So, Winnie K. W., Leung, Doris Y. P., Sham, Michael M. K., Tsui, Stephen K. W., Chan, Carmen W. H.
• Format: Article
• Language: English
• Subjects: A549 Cells; Activation; Activation analysis; Biomarkers; Cancer; Consolidation; crystalline silica; Data analysis; Data processing; Deoxyribonucleic acid; Disease control; DNA; DNA-binding protein; DNA‐binding inhibitor; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Exposure; Fibrosis; Gene expression; Gene Expression Regulation; Gene Library; Genes; Humans; Immune response; Immune system; In vitro methods and tests; Inhibitor of Differentiation Proteins - genetics; Inhibitor of Differentiation Proteins - metabolism; Inhibitors; Latency; Libraries; Lung - cytology; Lung - drug effects; Lungs; Macrophages; Occupational diseases; Pathogenesis; Polymerase chain reaction; Quartz; Reproducibility of Results; Ribonucleic acid; RNA; Sequence Analysis, RNA; Silica; Silicon dioxide; Silicon Dioxide - pharmacology; Silicosis; Silicosis - genetics; Transcriptome
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3471

Silicosis is a prolonged, irreversible and incurable occupational disease, and there is a significant number of newly diagnosed cases every year in Hong Kong. Due to the long latency of the disease, the diagnosis can be missed until detailed clinical examination at a later stage. For a better control of this deadly disease, detailing the pro‐inflammatory and fibrotic events in the macrophage would be instrumental in understanding the pathogenesis of the disease and essential for the significant biomarkers discovery. In this in vitro study, human cell line model A549 lung epithelial cells were used. The immediate molecular events underneath the activation of quartz silica polymorphs were followed in a time course of 0, 0.5, 2, 8, 16 and 24 h. The transcriptome library was prepared and subjected to RNA‐Seq analysis. Data analysis was performed by pathway analysis tools and verified by real‐time PCR. The results showed that triggered genes were mainly found in the immune response and inflammatory pathways. An interesting finding was the association of the DNA‐binding protein inhibitor (ID) family in the silica exposure to lung cells. The linkage of ID1, ID2 and ID3 to cancer may rationalize themselves to be the markers indicating an early response of silicosis. However, further studies are required to consolidate the roles of these genes in silicosis. Copyright © 2017 John Wiley & Sons, Ltd. In this study, human cell line A549 lung epithelial cells was used to investigate the immediate molecular events underneath the activation of quartz silica. The results showed that triggered genes were mainly found in immune response and inflammatory pathways. An interesting finding was the association of DNA‐binding protein inhibitor (ID) family in the silica exposure to lung cells. The linkage of ID1, ID2 and ID3 to cancer may rationalize themselves to be the markers indicating early response of silicosis.