Silver nanoparticles (AgNPs) are used in food packaging materials, dental care products and other consumer goods and can result in oral exposure. To determine whether AgNP coatings modulate transcriptional responses to AgNP exposure, we exposed mice orally to 20 nm citrate (cit)-coated AgNPs (cit-AgNPs) or polyvinylpyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) at a 4 mg/kg dose for 7 consecutive days and analyzed changes in the expression of protein-coding genes and long noncoding RNAs (lncRNAs), a new class of regulatory RNAs, in the liver. We identified unique and common expression signatures of protein-coding and lncRNA genes, altered biological processes and signaling pathways, and coding-non-coding gene interactions for cit-AgNPs and PVP-AgNPs. Commonly regulated genes comprised only about 10 and 20 percent of all differentially expressed genes in PVP-AgNP and cit-AgNP exposed mice, respectively. Commonly regulated biological processes included glutathione metabolic process and cellular oxidant detoxification. Commonly regulated pathways included Keap-Nrf2, PPAR, MAPK and IL-6 signaling pathways. The coding-non-coding gene co-expression analysis revealed that protein-coding genes were co-expressed with a variable number of lncRNAs ranging from one to twenty three and may share functional roles with the protein-coding genes. PVP-AgNP exposure induced a more robust transcriptional response than cit-AgNP exposure characterized by more than two-fold higher number of differentially expressed both protein- coding and lncRNA genes. Our data demonstrate that the surface coating strongly modulates the spectrum and the number of differentially expressed genes after oral AgNP exposure. On the other hand, our data suggest that AgNP exposure can alter drug and chemical sensitivity, metabolic homeostasis and cancer risk irrespective of the coating type, warranting further investigations.

中文翻译：

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表面涂层改变口腔暴露后对银纳米粒子的转录反应

银纳米粒子 (AgNPs) 用于食品包装材料、牙科护理产品和其他消费品，并可能导致口腔接触。为了确定 AgNP 涂层是否调节对 AgNP 暴露的转录反应，我们将小鼠口服暴露于 4 mg/kg 的 20 nm 柠檬酸盐 (cit) 包覆的 AgNPs (cit-AgNPs) 或聚乙烯吡咯烷酮 (PVP) 包覆的 AgNPs (PVP-AgNPs)连续 7 天给药，并分析了肝脏中蛋白质编码基因和长链非编码 RNA (lncRNA)（一类新的调节性 RNA）表达的变化。我们确定了 cit-AgNPs 和 PVP-AgNPs 的蛋白质编码和 lncRNA 基因的独特和常见的表达特征、改变的生物过程和信号通路，以及编码-非编码基因的相互作用。在 PVP-AgNP 和 cit-AgNP 暴露小鼠中，通常调控的基因仅占所有差异表达基因的 10% 和 20%。通常受监管的生物过程包括谷胱甘肽代谢过程和细胞氧化剂解毒过程。通常受调控的通路包括 Keap-Nrf2、PPAR、MAPK 和 IL-6 信号通路。编码-非编码基因共表达分析表明，蛋白质编码基因与数量不等的 lncRNA 共表达，范围从 1 到 23，并且可能与蛋白质编码基因共享功能作用。PVP-AgNP 暴露诱导了比 cit-AgNP 暴露更强大的转录反应，其特征是蛋白质编码和 lncRNA 基因的差异表达数量高出两倍以上。我们的数据表明，在口服 AgNP 暴露后，表面涂层强烈调节光谱和差异表达基因的数量。另一方面，我们的数据表明，无论涂层类型如何，AgNP 暴露都会改变药物和化学敏感性、代谢稳态和癌症风险，值得进一步研究。