Integrative functional transcriptomic analyses implicate specific molecular pathways in pulmonary toxicity from exposure to aluminum oxide nanoparticles

Nanotoxicology
Xiaobo LiRui Chen

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 kn...Continue Reading

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Citations

Nov 22, 2017·Journal of Nanobiotechnology·Eleonore Fröhlich
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Xiaobo LiRui Chen
Jan 7, 2020·Current Drug Metabolism·Pooja MalaviyaAbhay R Vasavada
Nov 2, 2018·Journal of Nanobiotechnology·Bella B ManshianStefaan J Soenen
Jan 17, 2019·Journal of Food and Drug Analysis·Xiaojia HeHuey-Min Hwang

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