Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene
Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:58 |
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| Enthalten in: |
Environmental science & technology - 58(2024), 14 vom: 09. Apr., Seite 6083-6092 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Yingyan [VerfasserIn] |
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| Links: |
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| Themen: |
1-NP |
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| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.est.3c07195 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370366603 |
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| 520 | |a Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses | ||
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| 700 | 1 | |a Chen, Yanyan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Yifei |e verfasserin |4 aut | |
| 700 | 1 | |a Diao, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Chiu, Raymond |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Jiacheng |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Yuting |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Zongwei |e verfasserin |4 aut | |
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