title: The induction of epigenetic regulation of PROS1 gene in lung fibroblasts by gold nanoparticles and implications for potential lung injury.
abstract: Advances in nanotechnology have given rise to the rapid development of novel applications in biomedicine. However, our understanding in the risks and health safety of nanomaterials is still not complete and various investigations are ongoing. Here, we show that gold nanoparticles (AuNPs) significantly altered the expression of 19 genes in human fetal lung fibroblasts (using the Affymetrix Human Gene 1.0 ST Array). Among the differentially expressed genes, up-regulation of microRNA-155 (miR-155) was observed concomitant with down-regulation of the PROS1 gene. Silencing of miR-155 established PROS1 as its possible target gene. DNA methylation profiling analysis of the PROS1 gene revealed no changes in the methylation status of this gene in AuNP-treated fibroblasts. At the ultrastructural level, chromatin condensation and reorganization was observed in the nucleus of fibroblasts exposed to AuNPs. The findings provide further insights into the molecular mechanisms underlying toxicity of AuNPs and their impact on epigenetic processes.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Cheng-Teng
authors.initials: CT
authors.lastname: Ng
authors.forename: S Thameem
authors.initials: ST
authors.lastname: Dheen
authors.forename: Wai-Cheong G
authors.initials: WC
authors.lastname: Yip
authors.forename: Choon-Nam
authors.initials: CN
authors.lastname: Ong
authors.forename: Boon-Huat
authors.initials: BH
authors.lastname: Bay
authors.forename: Lin-Yue
authors.initials: LY
authors.lastname: Lanry Yung
mesh_terms: D001798:Blood Proteins / Q000235:genetics*; D002460:Cell Line; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000378:metabolism*; D006046:Gold / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D008168:Lung / Q000166:cytology*; D035683:MicroRNAs / Q000235:genetics; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D017293:Protein S; D015854:Up-Regulation
chemical_list: D001798:Blood Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C523390:PROS1 protein, human; D017293:Protein S; D006046:Gold