Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals and O3 Exposure
2.2. Pulmonary Function Testing
2.3. Measurement of Lung Inflammation
2.3.1. Histopathological Staining of Lung
2.3.2. Collection and Analysis of BALF
2.4. Transcriptomics
Analysis of Differential Expression
2.5. Untargeted Metabolomics
2.5.1. Sample Extraction
2.5.2. Liquid Chromatography Conditions
2.5.3. Mass Spectrum Conditions
2.5.4. Differential Metabolism Analysis
2.6. Statistical Analyses
3. Results
3.1. O3 Induces Pulmonary Inflammatory Injury in Mice
3.2. Effect of O3 Exposure on Transcriptomics of Lung Tissues in Mice
3.3. Effects of O3 Exposure on Lung Tissue Metabolomics in Mice
3.4. Combined Analysis of Transcriptomics and Metabolomics
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AHR | Airway hyperresponsiveness |
BALF | Bronchoalveolar Lavage Fluid |
CC16 | Clara Cell Secretory Protein 16 |
DEGs | Differentially Expressed Genes |
DEMs | Differential metabolites |
FA | Filtered Air (Control Group) |
GO | Gene Ontology |
IL-6 | Interleukin-6 |
IL-1β | Interleukin-1β |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
LC-MS | Liquid Chromatography-Mass Spectrometry |
O-PEA | O-Phosphoethanolamine |
PAU | Pause |
PC | Phosphorylcholine |
Penh | Enhanced Pause |
Pla2g10 | Phospholipase A2 Group X |
PLS-DA | Partial Least Squares-Discriminant Analysis |
OPLS-DA | Orthogonal PLS-DA |
SPF | Specific Pathogen-Free |
Tr | Relaxation Time |
TV | Tidal Volume |
VIP | Variable Importance in Projection |
WBP | Whole Body Plethysmography |
PPAR | Peroxisome Proliferator-Activated Receptor |
Pla2g2c | Phospholipase A2 group IIC |
HMDB | Human Metabolome Database |
ELISA | Enzyme-linked immunosorbent assay |
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Pathway | Differential Metabolites | Differential Gene | p Value |
---|---|---|---|
Protein digestion and absorption | L-Glutamic acid; L-Histidine; L-Valine; Tyramine | Col24a1 | 0.0024 |
Glutathione metabolism | L-Glutamic acid; Spermidine; Pyroglutamic acid | Gsta1; Gsta5 | 0.0109 |
Glycerophospholipid metabolism | O-Phosphoethanolamine; Phosphorylcholine; Choline; | Pla2g10; Pla2g2c | 0.0255 |
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Zhou, X.; Guo, Y.; Jian, X.; Miao, X.; Wang, P.; Wang, X.; Wang, L.; Chen, H.; Feng, F. Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics. Toxics 2025, 13, 271. https://doi.org/10.3390/toxics13040271
Zhou X, Guo Y, Jian X, Miao X, Wang P, Wang X, Wang L, Chen H, Feng F. Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics. Toxics. 2025; 13(4):271. https://doi.org/10.3390/toxics13040271
Chicago/Turabian StyleZhou, Xiaolei, Yunnian Guo, Xiaotong Jian, Xinyi Miao, Pengpeng Wang, Xiaoke Wang, Ling Wang, Huaiyong Chen, and Feifei Feng. 2025. "Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics" Toxics 13, no. 4: 271. https://doi.org/10.3390/toxics13040271
APA StyleZhou, X., Guo, Y., Jian, X., Miao, X., Wang, P., Wang, X., Wang, L., Chen, H., & Feng, F. (2025). Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics. Toxics, 13(4), 271. https://doi.org/10.3390/toxics13040271