title: Integrative functional transcriptomic analyses implicate specific molecular pathways in pulmonary toxicity from exposure to aluminum oxide nanoparticles.
abstract: Gene expression profiling has developed rapidly in recent years and it can predict and define mechanisms underlying chemical toxicity. Here, RNA microarray and computational technology were used to show that aluminum oxide nanoparticles (Al2O3 NPs) were capable of triggering up-regulation of genes related to the cell cycle and cell death in a human A549 lung adenocarcinoma cell line. Gene expression levels were validated in Al2O3 NPs exposed A549 cells and mice lung tissues, most of which showed consistent trends in regulation. Gene-transcription factor network analysis coupled with cell- and animal-based assays demonstrated that the genes encoding PTPN6, RTN4, BAX and IER play a role in the biological responses induced by the nanoparticle exposure, which caused cell death and cell cycle arrest in the G2/S phase. Further, down-regulated PTPN6 expression demonstrated a core role in the network, thus expression level of PTPN6 was rescued by plasmid transfection, which showed ameliorative effects of A549 cells against cell death and cell cycle arrest. These results demonstrate the feasibility of using gene expression profiling to predict cellular responses induced by nanomaterials, which could be used to develop a comprehensive knowledge of nanotoxicity.
authors.affiliation: a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China .
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China .
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: b Department of Toxicology and Function Assessment , Jiangsu Provincial Center for Disease Prevention and Control , Nanjing , China .
authors.forename: Qian
authors.initials: Q
authors.lastname: Bian
authors.affiliation: c Institute of Bioinformatics, Heinrich Heine University , Dusseldorf , Germany .
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China .
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China .
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Meng
authors.affiliation: a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China .
authors.forename: Shenshen
authors.initials: S
authors.lastname: Wu
authors.affiliation: a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China .
authors.forename: Shizhi
authors.initials: S
authors.lastname: Wang
authors.affiliation: d Key Laboratory of Modern Toxicology of Ministry of Education , School of Public Health, Nanjing Medical University , Nanjing , China , and.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: a Key Laboratory of Environmental Medicine Engineering, Ministry of Education , School of Public Health, Southeast University , Nanjing , China .|e State Key Laboratory of Bioelectronics , Southeast University , Nanjing , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D000537:Aluminum Oxide / Q000737:chemistry / Q000633:toxicity*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008168:Lung / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000537:Aluminum Oxide
keywords: Aluminum oxide nanoparticle; cell cycle; cell death; microarray; nanotoxicology