Genome-wide transcriptional analysis of cardiovascular-related genes and pathways induced by PM2.5 in human myocardial cells
Genome-wide transcriptional analysis of cardiovascular-related genes and pathways induced by PM2.5 in human myocardial cells
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PM2.5诱导人心肌细胞心血管相关基因和通路的全基因组转录分析
DOI：
10.1007/s11356-017-8773-3
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发表时间：
2017-04-01
影响因子：
5.8
通讯作者：
Sun, Zhiwei
中科院分区：
文献类型：
--
作者：
Feng, Lin;Yang, Xiaozhe;Sun, Zhiwei
空气污染一直是与环境有关的主要健康威胁。大多数关于PM2.5毒性的研究都证实了PM2.5对心血管系统和内皮细胞的毒性。然而，关于pm2.5引起的心肌相关毒性的研究有限。本研究旨在通过微阵列分析和生物信息学分析，全面了解PM2.5对人心肌细胞（AC16）的毒性作用，探讨其分子机制。微阵列数据分析显示，与对照组相比，pm2.5诱导的毒性影响了472个基因的表达，其中166个基因在人心肌（AC16）细胞中表达上调，306个基因表达下调。氧化石墨烯分析显示，免疫反应、细胞成熟、胚胎心管形态发生、细胞对电刺激的反应、骨骼肌组织再生和信号转导的负调控等细胞过程上调，而转录（dna依赖性）、节律过程、蛋白质不稳定凋亡过程和先天免疫反应的调控下调。通路分析表明，细胞因子-细胞因子受体相互作用、NF-κB信号通路、趋化因子信号通路、内分泌等因子调控的钙重吸收、HTLV-I感染、细胞粘附分子（CAMs）等细胞信号通路上调，TGF-β信号通路下调。此外，Signal-net显示，与对照组相比，TUBA4A、ADRBK2、BRIX1、SMC4、EIF5B、PRMT1、ATG4B和NDC80基因的表达量显著降低，而KRT6B基因的表达量显著增加。所有基因均经qRT-PCR验证。本研究为pm2.5心肌组织毒性研究提供了新的生物信息学依据，为进一步开展心血管系统毒性研究奠定了基础。
Air pollution has been a major environment-related health threat. Most of the studies on PM2.5 toxicity have verified on the cardiovascular system and endothelial cells. However, researches on PM2.5-induced myocardial-related toxicity are limited. This study aims to fully understand the toxic effects of PM2.5 on human myocardial cell (AC16) and explore its molecular mechanism based on microarray analysis and bioinformatics analysis. Microarray data analysis manifested that PM2.5-induced toxicity affected expression of 472 genes compared with the control group, including 166 upregulated genes and 306 downregulated genes in human myocardial (AC16) cells. GO analysis showed that cellular processes such as immune response, cell maturation, embryonic heart tube morphogenesis, cellular response to electrical stimulus, skeletal muscle tissue regeneration, and negative regulation of signal transduction were upregulated, while regulation of transcription (DNA-dependent), rhythmic process, protein destabilization apoptotic process, and innate immune response were downregulated. The pathway analysis indicates that cell signaling pathways such as cytokine-cytokine receptor interaction, NF-κB signaling pathway, chemokine signaling pathway, endocrine and other factor-regulated calcium reabsorption, HTLV-I infection, and cell adhesion molecules (CAMs) were upregulated, while the TGF-β signaling pathway was downregulated. In addition, Signal-net showed that the TUBA4A, ADRBK2, BRIX1, SMC4, EIF5B, PRMT1, ATG4B, and NDC80 genes were significantly decreased, while the expression of the KRT6B gene was markedly increased compared with the control group. All the genes were verified by qRT-PCR. This study had provided new bioinformatics evidences in PM2.5-induced myocardial tissue toxicity which is necessary for further cardiovascular system toxicity studies.