Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Department of Infectious Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Environ Sci Pollut Res Int. 2021 Feb;28(8):9598-9609. doi: 10.1007/s11356-020-11347-1. Epub 2020 Nov 5.
Urban particulate matter (PM), a great danger to public health, is associated with increasing risk of pulmonary diseases. However, the involved key genes and signaling pathways mediating the cellular responses to urban PM are largely unknown. In this study, human bronchial epithelial cells BEAS-2B was exposed to Standard reference material (SRM) 1649b, followed by RNA-sequencing (RNA-seq) and a combination of different bioinformatics analysis. A total of 201 genes (111 upregulated and 90 downregulated) were identified as the differentially expressed genes (DEGs). Moreover, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) unveiled several significant genes and pathways involved in PM-induced lung toxicity. Protein-protein interaction (PPI) network was performed with the Search Tool for the Retrieval of Interacting Genes (STRING), and the hub gene modules were recognized by Molecular Complex Detection (MCODE), a plug-in of Cytoscape. Moreover, Connectivity Map (CMap) analysis found six candidate small molecular compounds to reverse PM-altered gene expression, including aminohippuric acid, captopril, cinoxacin, fasudil, pargyline, and altizide. Finally, the expressions of part vital genes related to inflammation (IL-1β, CXCL2, CXCL5, CXCL8), ferroptosis (HMOX1, GCLM), and autophagy (BECN1, MAPK1LC3B) were in accordance with the RNA-seq data, with a concentration-dependent manner. This study may be helpful in revealing the complex molecular mechanisms underlying PM-induced lung toxicity and provide some new therapeutic targets for PM-related pulmonary diseases.
城市颗粒物（PM）对公众健康构成巨大威胁，与肺部疾病风险增加有关。然而，介导细胞对城市 PM 反应的关键基因和信号通路尚不清楚。在这项研究中，用人支气管上皮细胞 BEAS-2B 暴露于标准参考物质（SRM）1649b 后，进行 RNA 测序（RNA-seq）和多种不同的生物信息学分析。共鉴定出 201 个差异表达基因（111 个上调和 90 个下调）。此外，基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）揭示了几个参与 PM 诱导肺毒性的重要基因和途径。蛋白质-蛋白质相互作用（PPI）网络使用 Search Tool for the Retrieval of Interacting Genes（STRING）进行，分子复合物检测（MCODE）是 Cytoscape 的一个插件，用于识别枢纽基因模块。此外，Connectivity Map（CMap）分析发现了六种候选小分子化合物来逆转 PM 改变的基因表达，包括氨苯蝶啶、卡托普利、西诺沙星、法舒地尔、帕吉林和阿替唑嗪。最后，部分与炎症（IL-1β、CXCL2、CXCL5、CXCL8）、铁死亡（HMOX1、GCLM）和自噬（BECN1、MAPK1LC3B）相关的重要基因的表达与 RNA-seq 数据一致，呈浓度依赖性。这项研究可能有助于揭示 PM 诱导肺毒性的复杂分子机制，并为 PM 相关肺部疾病提供一些新的治疗靶点。
