Genome wide identification and expression profile in epithelial cells exposed to TiO2 particles

• Published in: Environmental toxicology 2015-03, Vol.30 (3), p.293-300
• Main Authors: Kim, Tae‐Hoon, Shin, Seung‐Woo, Park, Jong‐Sook, Park, Choon‐Sik
• Format: Article
• Language: English
• Subjects: bioinformatics; biosynthesis; Cell Line; Computational Biology; epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; gene; gene expression; Gene Expression - drug effects; gene expression profile; gene expression regulation; Gene Expression Regulation - drug effects; genes; Genome-Wide Association Study; Humans; inflammation; ITGAV; messenger RNA; microarray technology; Nanoparticles - toxicity; Polymerase Chain Reaction; quantitative polymerase chain reaction; respiratory tract diseases; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Titanium - toxicity; titanium dioxide
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.21906

Environmental particles are believed to provoke airway inflammation in susceptible individuals by stimulating epithelial cells to release mediators that exacerbate lung diseases. Here, we sought to identify genes expressed throughout the genome by epithelial cells stimulated with TiO₂particles. A human bronchial epithelial cell line, BEAS‐2B, was stimulated with or without 40 µg TiO₂for 2 h. RNA was purified from cells and subjected to microarray analysis. Genes exhibiting more than a twofold change in RNA expression were selected. Candidate genes were then analyzed using bioinformatics tools, including pathway, ontology, and network analyses. ITGAV mRNA expression levels were measured in BEAS‐2B cells using real‐time polymerase chain reaction. Among 37,803 genes, 92 genes displayed more than a twofold change in mRNA levels according to the microarray analysis; 87 genes were upregulated while five genes were downregulated. The 92 genes were classified based on functional annotation using a protein information resource database search for biological processes and a pathway search using the KEGG pathway database. These genes are related to macromolecule biosynthesis, metabolic processes and, in particular, RNA metabolism. When genes with more than a threefold change were analyzed, KIF11, ITGAV, SEMA3C, IBTK, and DEK were selected as candidate genes induced by TiO₂‐stimulated BEAS‐2B cells. To validate these results, BEAS‐2B cells stimulated with 40 µg TiO₂expressed threefold higher ITGAV mRNA levels compared to those without TiO₂particle stimulation. We conclude that KIF11, ITGAV, SEMA3C, IBTK, and DEK are candidate genes expressed by epithelial cells when stimulated with TiO₂particles. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 293–300, 2015.