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: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| 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. |
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| ISSN: | 0147-6513 |