State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
J Biomed Nanotechnol. 2011 Apr;7(2):263-75. doi: 10.1166/jbn.2011.1286.
The aim of this paper was to investigate the molecular mechanisms of interaction between nanosilver and human dermal fibroblasts-fetal (HDF-f) at the level of gene expression. After HDF-f was treated with nanosilver for 1, 4 and 8 h, the cellular response was evaluated with methylthiazoltetrazolium (MTT) assay and flow cytometry analysis. Global gene expression profiles were examined using Illumina Human-6_V3 Expression BeadChip Array and the results were verified by quantitative real-time polymerase chain reaction (RT-PCR). The obtained differential expressed genes were analyzed by the integration of clustering, gene ontology (GO) and biological pathway analysis. The results suggest that nanosilver may cause disruption of cytoskeleton and cellular membrane, disturbance of energy metabolism and gene expression associated pathways, and DNA damage accompanied by cell cycle arrest. When the nanoparticle-cell interaction mechanisms induced by nanogold in our previous research were compared with nanosilver in the present study, both the similarities and differences underlying biological processes and gene regulations were found. The research also suggests that the genomics research can provide a convenient and efficient approach to the understanding of cytotoxicity mechanisms of nanomaterials.
本研究旨在探讨纳米银与人类真皮成纤维细胞-胎儿(HDF-f)在基因表达水平上相互作用的分子机制。用纳米银处理 HDF-f1、4 和 8 小时后,用噻唑蓝(MTT)比色法和流式细胞术分析评估细胞反应。采用 Illumina Human-6_V3 Expression BeadChip Array 检测全基因组表达谱,并通过实时定量聚合酶链反应(RT-PCR)进行验证。通过聚类、基因本体(GO)和生物通路分析对获得的差异表达基因进行分析。结果表明,纳米银可能导致细胞骨架和细胞膜破坏、能量代谢紊乱以及与基因表达相关的通路紊乱,还可能导致 DNA 损伤和细胞周期停滞。将本研究中纳米银与我们之前研究中纳米金诱导的纳米颗粒-细胞相互作用机制进行比较后发现,生物过程和基因调控存在相似和不同之处。研究还表明,基因组学研究可以为理解纳米材料的细胞毒性机制提供一种便捷、高效的方法。