posted on 2024-03-28, 17:37authored byYingyan Zhou, Cun Li, Yanyan Chen, Yifei Yu, Xin Diao, Raymond Chiu, Jiacheng Fang, Yuting Shen, Jianing Wang, Lin Zhu, Jie Zhou, Zongwei Cai
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.