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Transcriptomic analysis of key genes and pathways in human bronchial epithelial cells BEAS-2B exposed to urban particulate matter

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Abstract

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.

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Data Availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Funding

This study was supported by the State Key Basic Research Program project (2015CB553404), the National Natural Science Foundation of China (81630001, 81770075, 82041003), Science and Technology Commission of Shanghai Municipality (20411950402), Shanghai Municipal Key Clinical Specialty (shslczdzk02201) and Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02013), National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX09201002-006).

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  1. Mengchan Zhu and Jian Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China

    Mengchan Zhu, Jian Wang, Cuicui Chen & Yuanlin Song

  2. Department of Infectious Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China

    Mengchan Zhu & Jue Pan

Authors
  1. Mengchan Zhu
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  2. Jian Wang
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  3. Cuicui Chen
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  4. Yuanlin Song
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  5. Jue Pan
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Contributions

Jue Pan and Yuanlin Song designed and supervised the study. Mengchan Zhu, Jian Wang, and Cuicui Chen performed the experiments. Mengchan Zhu and Cuicui Chen analyzed and interpreted the data. Mengchan Zhu and Jian Wang drew the figures and wrote the manuscript.

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Correspondence to Yuanlin Song or Jue Pan.

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Zhu, M., Wang, J., Chen, C. et al. Transcriptomic analysis of key genes and pathways in human bronchial epithelial cells BEAS-2B exposed to urban particulate matter. Environ Sci Pollut Res 28, 9598–9609 (2021). https://doi.org/10.1007/s11356-020-11347-1

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