Single-cell RNA sequencing identifies cellular heterogeneity in endothelial and epithelial cells associated with nitrogen dioxide-induced acute lung injury

Inhalation of nitrogen dioxide (NO2), a representative irritant gas, can trigger acute lung injury (ALI), typically characterized by increased permeability and dysfunction of the blood-air barrier. However, the exact mechanisms underlying NO2 inhalation-induced ALI (NO2-ALI) remain poorly understood...

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Main Authors: Weidong Li, Zhenghao Bao, Hongpeng Huang, Yingkai Ma, Yangyang Sun, Xueyang Lin, Weiqiang Sun, Shengran Wang, Ziqi Cui, Chen Yang, Yufeng Yang, Simin Lang, Zheming Yuan, Yongan Wang, Yuan Luo
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325007213
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Summary:Inhalation of nitrogen dioxide (NO2), a representative irritant gas, can trigger acute lung injury (ALI), typically characterized by increased permeability and dysfunction of the blood-air barrier. However, the exact mechanisms underlying NO2 inhalation-induced ALI (NO2-ALI) remain poorly understood. Using single-cell RNA sequencing (scRNA-seq), we identified significant alterations in endothelial and epithelial cells during NO2-ALI. Notably, leucine-rich alpha-2-glycoprotein 1 (Lrg1) and uncoupling protein 2 (Ucp2), which have been implicated in ALI progression, were significantly upregulated in endothelial cells following NO2 exposure (P < 0.05 compared to control). General capillaries (GCs) potentially function as stem cells, facilitating endothelial cell repair and recruiting neutrophils to amplify inflammatory responses. Furthermore, a novel subpopulation of epithelial cells, identified as lymphocyte antigen 6 A+ (Ly6a) alveolar cells, showed a significant increase in abundance (P < 0.05 compared to control) and played a pivotal role in alveolar epithelial cell differentiation after NO2 inhalation. Overall, these findings shed insights into the pathogenic roles of endothelial and epithelial cells in NO2-ALI.
ISSN:0147-6513