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二氧化硅纳米颗粒对斑马鱼胚胎毒性的全基因组转录分析。

Genome-wide transcriptional analysis of silica nanoparticle-induced toxicity in zebrafish embryos.

作者信息

Hu Hejing, Li Qiuling, Jiang Lizhen, Zou Yang, Duan Junchao, Sun Zhiwei

机构信息

Department of Toxicology and Sanitary Chemistry , School of Public Health , Capital Medical University , Beijing 100069 , P.R. China.

Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , Beijing 100069 , P.R. China . Email:

出版信息

Toxicol Res (Camb). 2016 Jan 20;5(2):609-620. doi: 10.1039/c5tx00383k. eCollection 2016 Mar 1.

Abstract

Although silica nanoparticles (SiNPs) have a promising application in biomedical fields, there is still a lack of comprehensive understanding of genome-wide transcriptional analysis. This study aims to clarify the toxic effect and molecular mechanisms of SiNPs in zebrafish embryos based on microarray analysis and bioinformatics analysis. Microarray data analysis demonstrated that SiNP-induced toxicity in zebrafish embryos affected expression of 2515 genes, including 1107 genes that were up-regulated and 1408 genes that were down-regulated. These differentially expressed genes were subjected to bioinformatics analysis for exploring the biological processes triggered by SiNPs in zebrafish embryos. Gene ontology analysis showed that SiNPs caused significant changes in gene expression patterns related to many important functions, including response to stimuli, immune response, cellular processes, and embryonic development. In addition, pathway analysis and Signal-net analysis indicated that the gap junction, vascular smooth muscle contraction, and metabolic pathways, apoptosis, the MAPK signaling pathway, the calcium signaling pathway and the JAK-STAT signaling pathway were the most prominent significant pathways in SiNP-induced toxicity in zebrafish embryos. In addition, the results from qRT-PCR and western blot analysis showed that the IL-6 dependent JAK1/STAT3 signaling pathway was activated by SiNPs in zebrafish embryos. In summary, our data will provide compelling clues for further exploration of SiNP-induced toxicity in zebrafish embryos.

摘要

尽管二氧化硅纳米颗粒(SiNPs)在生物医学领域有着广阔的应用前景,但目前对全基因组转录分析仍缺乏全面的了解。本研究旨在通过微阵列分析和生物信息学分析,阐明SiNPs对斑马鱼胚胎的毒性作用及其分子机制。微阵列数据分析表明,SiNP诱导的斑马鱼胚胎毒性影响了2515个基因的表达,其中1107个基因上调,1408个基因下调。对这些差异表达基因进行生物信息学分析,以探索SiNPs在斑马鱼胚胎中引发的生物学过程。基因本体分析表明,SiNPs导致与许多重要功能相关的基因表达模式发生显著变化,包括对刺激的反应、免疫反应、细胞过程和胚胎发育。此外,通路分析和信号网络分析表明,缝隙连接、血管平滑肌收缩和代谢途径、凋亡、MAPK信号通路、钙信号通路和JAK-STAT信号通路是SiNP诱导斑马鱼胚胎毒性中最显著的重要通路。此外,qRT-PCR和蛋白质印迹分析结果表明,SiNPs在斑马鱼胚胎中激活了IL-6依赖性JAK1/STAT3信号通路。总之,我们的数据将为进一步探索SiNP诱导的斑马鱼胚胎毒性提供有力线索。

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