Hu Hejing, Asweto Collins Otieno, Wu Jing, Shi Yanfeng, Feng Lin, Yang Xiaozhe, Liang Shuang, Cao Lige, Duan Junchao, Sun Zhiwei
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
Chemosphere. 2017 Sep;183:589-598. doi: 10.1016/j.chemosphere.2017.05.153. Epub 2017 May 27.
Cardiovascular system is demonstrated the main target of PM and the objective of this study was to explore the toxic effect and molecular mechanisms caused by PM in primary human umbilical vein endothelial cells (HUVECs) using microarray and bioinformatics analysis. The results showed that 591 genes were differentially expressed triggered by PM, of which 174 genes were down-regulated, while 417 genes were up-regulated. Gene ontology analysis revealed that PM caused significant changes in gene expression patterns, including response to stimuli, immune response, and cellular processes. Pathway analysis and Signal-net analysis suggested that endocytosis, chemokine signaling pathway, RNA transport, protein processing in endoplasmic reticulum (ER) and autophagy regulation were the most critical pathways in PM-induced toxicity in HUVECs. Moreover, gene expression confirmation of LIF, BCL2L1, CSF3, HMOX1, RPS6, PFKFB, CAPN1, HSPBP1, MOGS, PREB, TUBB2A, GABARAP by qRT-PCR indicated that endocytosis might be involved in the cellular uptake of PM by forming phagosomes, and subsequently inflammation, hypoxia and ER stress was occurred, which finally activated autophagy after PM exposure in HUVECs. In summary, our data can serve as fundamental research clues for further studies of PM-induced toxicity in HUVECs.
心血管系统被证明是颗粒物（PM）的主要作用靶点，本研究的目的是利用微阵列和生物信息学分析，探讨PM对人脐静脉内皮细胞（HUVECs）的毒性作用及其分子机制。结果显示，PM引发了591个基因的差异表达，其中174个基因下调，417个基因上调。基因本体分析表明，PM导致基因表达模式发生显著变化，包括对刺激的反应、免疫反应和细胞过程。通路分析和信号网络分析表明，内吞作用、趋化因子信号通路、RNA转运、内质网（ER）中的蛋白质加工和自噬调节是PM诱导HUVECs毒性的最关键通路。此外，通过qRT-PCR对LIF、BCL2L1、CSF3、HMOX1、RPS6、PFKFB、CAPN1、HSPBP1、MOGS、PREB、TUBB2A、GABARAP基因表达的验证表明，内吞作用可能通过形成吞噬体参与PM的细胞摄取，随后发生炎症、缺氧和内质网应激，最终在PM暴露于HUVECs后激活自噬。总之，我们的数据可为进一步研究PM对HUVECs的毒性作用提供基础研究线索。
