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金纳米颗粒对人真皮成纤维细胞影响的全球基因表达分析。

Global gene expression analysis of the effects of gold nanoparticles on human dermal fibroblasts.

机构信息

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.

出版信息

J Biomed Nanotechnol. 2010 Jun;6(3):234-46. doi: 10.1166/jbn.2010.1128.

Abstract

In order to investigate the molecular effects of gold nanoparticles (GNPs) and cell interaction, after human dermal fibroblasts-fetal (HDF-f) treated with GNPs for 1, 4 and 8 h, the cytotoxicity was evaluated with methylthiazoltetrazolium (MTT) assay. Flow cytometry experiment was used to assess effects of GNPs on cell cycle and apoptosis. Differentially expressed genes in HDF-f treated with GNPs were obtained using gene expression profile microarray. The gene differential expression profile was analyzed by clustering, Gene Ontology (GO) and biological pathway. The results from these analyses were integrated to comprehensively interpret the data gained from microarray. It suggests that the exposure of HDF-f to GNPs might lead to the disturbance of cell cycle regulation, cellular oxidative stress and affect regulation of actin cytoskeleton, and other cellular activities such as cell adhesion, energy metabolism and signal transduction may be also affected. Compared with the cytotoxicological mechanisms induced by Ni2+ from our previous research and by GNPs from the present study, different underlying biological processes and gene regulations were found. The integration of microarray and bioinformatics analysis can provide a specific and efficient routine to discuss molecular effects of cellular response to biomaterials.

摘要

为了研究金纳米粒子(GNPs)与细胞相互作用的分子效应,用人真皮成纤维细胞-胎儿(HDF-f)经 GNPs 处理 1、4 和 8 h 后,用噻唑蓝(MTT)法评估细胞毒性。用流式细胞术实验评估 GNPs 对细胞周期和凋亡的影响。用基因表达谱微阵列获得经 GNPs 处理的 HDF-f 中的差异表达基因。通过聚类、基因本体论(GO)和生物途径分析差异表达基因的基因差异表达谱。将这些分析的结果整合起来,全面解释微阵列获得的数据。结果表明,HDF-f 暴露于 GNPs 可能导致细胞周期调控紊乱、细胞氧化应激,并影响肌动蛋白细胞骨架的调节,以及细胞黏附、能量代谢和信号转导等其他细胞活动也可能受到影响。与我们之前的研究中 Ni2+和本研究中 GNPs 诱导的细胞毒性机制相比,发现了不同的潜在生物学过程和基因调控。微阵列和生物信息学分析的整合可以提供一种特定而有效的常规方法来讨论细胞对生物材料反应的分子效应。

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