Toxicology of respiratory system: Profiling chemicals in PM10 for molecular targets and adverse outcomes

文献类型： 外文期刊

第一作者： Wang, Junyu

作者： Wang, Junyu;Zhang, Yixia;Li, Ang;Gao, Xin;Lv, Danyu;Zheng, Huaize;Kou, Xiaohong;Xue, Zhaohui;Zhang, Zhijun;Yu, Wancong

作者机构：

关键词： PM10; Respiratory system injury; Bioinformatics analysis; Molecular targets; Signaling pathway

期刊名称：ENVIRONMENT INTERNATIONAL （ 影响因子：13.352； 五年影响因子：13.238 ）

ISSN： 0160-4120

年卷期： 2022 年 159 卷

页码：

收录情况： SCI

摘要： Numerous studies have shown that the increasing trend of respiratory diseases have been closely associated with the endogenous toxic chemicals (polycyclic aromatic hydrocarbons, heavy metal ions, etc.) in PM10. In the present study, we aim to determine the strong correlations between the chemicals in PM10 and the adverse consequences. We used the ChemView DB, the ToxRef DB and a comprehensive literature analysis to collect, identify, and evaluate the chemicals in PM10 and their adverse effects on respiratory system, and then used the ToxCast DB to analyze their bioactivity and key targets through 1192 molecular targets and cell characteristic endpoints. Meanwhile, the bioinformatics analysis were carried out on the molecular targets to screen out prevention and treatment targets. A total of 310 chemicals related to the respiratory system were identified. An unsupervised two-directional heatmap was constructed based on hierarchical clustering of 227 chemicals by their effect scores. A subset of 253 chemicals with respiratory system toxicity had in vitro bioactivity on 318 molecular targets that could be described, clustered and annotated in the heatmap and bipartite network, which were analyzed based on the protein information in UniProt KB database and the software of GO, STRING, and KEGG. These results showed that the chemicals in PM10 have strong correlation with different types of respiratory system injury. The main pathways of respiratory system injury caused by PM10 are the Calcium signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway, and the core proteins in which are likely to be the molecular targets for the prevention and treatment of damage caused by PM10.

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