Microarray-assisted size-effect study of amorphous silica nanoparticles on human bronchial epithelial cells
Microarray-assisted size-effect study of amorphous silica nanoparticles on human bronchial epithelial cells
复制标题
无定形二氧化硅纳米颗粒对人支气管上皮细胞的微阵列辅助尺寸效应研究
DOI：
10.1039/c9nr07350g
复制
发表时间：
2019-12-21
期刊：
影响因子：
6.7
通讯作者：
Sun, Zhiwei
中科院分区：
文献类型：
--
作者：
Li, Yang;Duan, Junchao;Sun, Zhiwei
无定形二氧化硅纳米粒子（SiNPs）不仅在自然界中大量存在，而且是年产量第二大的工程纳米材料。呼吸道接触是SiNP进入人体的主要途径。大量的研究集中在SiNPs的呼吸毒性上，发现SiNPs可引起肺组织损伤、炎症、纤维化甚至支气管上皮细胞的恶性转化，但SiNPs的尺寸依赖性毒性及其潜在的生物学机制尚不清楚。在这方面，转录组学研究将有助于更好地了解毒性机制。在本研究中，微阵列分析进行了调查的全基因组的转录改变诱导不同大小的SiNPs在人原代支气管上皮细胞（BEAS-2B）。为了确定粒度对毒性的影响，引入了两种尺寸（41 nm和61 nm）的纳米颗粒和一种尺寸（206 nm）的亚微米颗粒。生物信息学分析结果表明：（1）随着SiNP粒径的减小，3个SiNP处理组中差异表达基因的数量逐渐增多;（2）免疫和炎症反应、基因表达、信号转导、内质网应激、氧化应激、细胞代谢和细胞增殖等相关基因随着粒径的减小而逐渐上调，（3）两种纳米颗粒的作用方式有一定程度的重叠，与亚微米颗粒的作用方式存在许多不同;（4）两种二氧化硅纳米颗粒均影响与二氧化硅纳米颗粒进入细胞、自噬和溶酶体功能障碍、内质网应激、炎症反应、DNA损伤和基因表达以及凋亡抗性和癌症相关的途径。据我们所知，这是第一个研究报告的基因表达谱的变化趋势与二氧化硅颗粒大小的变化。我们的研究为SiNPs呼吸毒性机制提供了大量信息，也为SiNPs的毒性和安全性评价提供了实验依据。
Amorphous silica nanoparticles (SiNPs) are not only abundant in nature, but also the second largest engineering nanomaterials in terms of annual output. Respiratory exposure is the main route for SiNPs to enter the human body. A large number of studies have focused on the respiratory toxicity of SiNPs and demonstrated that SiNPs could induce pulmonary tissue damage, inflammation, fibrosis, and even the malignant transformation of bronchial epithelial cells, while the size-dependent toxicity of SiNPs and their underlying biological mechanisms remain unclear. In this regard, a transcriptomics study would be conductive to gaining a better understanding of the toxic mechanism. In the present study, microarray analysis was performed to investigate the genome-wide transcriptional alteration induced by different sizes of SiNPs in human primary bronchial epithelial cells (BEAS-2B). To determine the effect of the particle size on the toxicity, nanoparticles of two sizes (41 nm and 61 nm) and submicron particles of one size (206 nm) were introduced. The bioinformatics analysis results indicated that: (1) the number of differentially expressed genes in the three SiNP-treated groups increased with the particle size decreasing; (2) the genes involved in the immune and inflammatory response, gene expression, signal transduction, endoplasmic reticulum stress, oxidative stress, cell metabolism, and cell proliferation were gradually upregulated with the particle size decreasing, while the genes related to the morphological development of the respiratory system were gradually downregulated with the particle size decreasing; (3) the modes of action of the two nanoparticles overlapped with each other to some degree, and there existed many different modes compared to those from the submicron particles; (4) both the silica nanoparticles affected the pathways associated with the cell entry of silica nanoparticles, autophagy and lysosomal dysfunction, endoplasmic reticulum stress, inflammatory response, DNA damage, and gene expression, as well as apoptotic resistance and cancer. To the best of our knowledge, this is the first study that has reported the alteration trend of gene expression profiles with the change in silica particle size. Our study provides a great deal of information on the toxic mechanisms underlying the respiratory toxicity induced by SiNPs, and can also serve as an experimental basis for the toxicity and safety evaluation of silica nanoparticles.