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RNA-sequencing reveals long-term effects of silver nanoparticles on human lung cells
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
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Number of Authors: 52018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6668Article in journal (Refereed) Published
Abstract [en]

Despite a considerable focus on the adverse effects of silver nanoparticles (AgNPs) in recent years, studies on the potential long-term effects of AgNPs are scarce. The aim of this study was to explore the effects of AgNPs following repeated low-dose, long-term exposure of human bronchial epithelial cells. To this end, the human BEAS-2B cell line was exposed to 1 mu g/mL AgNPs (10 nm) for 6 weeks followed by RNA-sequencing (RNA-Seq) as well as genome-wide DNA methylation analysis. The transcriptomics analysis showed that a substantial number of genes (1717) were differentially expressed following AgNP exposure whereas only marginal effects on DNA methylation were observed. Downstream analysis of the transcriptomics data identified several affected pathways including the 'fibrosis' and 'epithelial-mesenchymal transition' (EMT) pathway. Subsequently, functional validation studies were performed using AgNPs of two different sizes (10 nm and 75 nm). Both NPs increased collagen deposition, indicative of fibrosis, and induced EMT, as evidenced by an increased invasion index, anchorage independent cell growth, as well as cadherin switching. In conclusion, using a combination of RNA-Seq and functional assays, our study revealed that repeated low-dose, long-term exposure of human BEAS-2B cells to AgNPs is pro-fibrotic, induces EMT and cell transformation.

Place, publisher, year, edition, pages
2018. Vol. 8, article id 6668
Keywords [en]
Chemical biology, Lung cancer, Risk factors
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-156658DOI: 10.1038/s41598-018-25085-5ISI: 000431003200005PubMedID: 29703973OAI: oai:DiVA.org:su-156658DiVA, id: diva2:1213245
Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-06-04Bibliographically approved

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