Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics

O<sub>3</sub> (ozone) is an environmental pollutant that can exacerbate inflammatory damage and contribute to respiratory diseases. However, the molecular mechanisms and potential targets for intervention in ozone-induced lung inflammatory injury are not yet known. To address this, our s...

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Main Authors: Xiaolei Zhou, Yunnian Guo, Xiaotong Jian, Xinyi Miao, Pengpeng Wang, Xiaoke Wang, Ling Wang, Huaiyong Chen, Feifei Feng
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Toxics
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Online Access:https://www.mdpi.com/2305-6304/13/4/271
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author Xiaolei Zhou
Yunnian Guo
Xiaotong Jian
Xinyi Miao
Pengpeng Wang
Xiaoke Wang
Ling Wang
Huaiyong Chen
Feifei Feng
author_facet Xiaolei Zhou
Yunnian Guo
Xiaotong Jian
Xinyi Miao
Pengpeng Wang
Xiaoke Wang
Ling Wang
Huaiyong Chen
Feifei Feng
author_sort Xiaolei Zhou
collection DOAJ
description O<sub>3</sub> (ozone) is an environmental pollutant that can exacerbate inflammatory damage and contribute to respiratory diseases. However, the molecular mechanisms and potential targets for intervention in ozone-induced lung inflammatory injury are not yet known. To address this, our study exposed mice to 0.6 ppm and 1.0 ppm of O<sub>3</sub> (3 h/d, 14 d), evaluating lung inflammation through histopathological examinations, lung function assessments, and analyses of white blood cells and inflammatory factors in BALF. Furthermore, we employed transcriptomic and non-targeted metabolomic approaches to decipher differentially expressed genes (DEGs) and metabolites in mouse lung tissue from the 1.0 ppm O<sub>3</sub> exposure group. A comprehensive integration analysis of these omics data was conducted using Pearson correlation analysis. Finally, our findings show that ozone exposure indeed elicits pulmonary inflammation. Transcriptomic analysis identified 311 differentially expressed genes, predominantly implicated in circadian rhythm, IL-17 signaling pathway, and PPAR signaling. Meanwhile, metabolomic profiling revealed 41 differentially regulated metabolites, mainly associated with riboflavin metabolism, glutathione metabolism, and ABC transporter pathways. Integrated multi-omics analysis through Pearson correlation identified three key components (Pla2g10, O-phosphoethanolamine, and phosphorylcholine) showing significant enrichment in glycerophospholipid metabolism. Collectively, our findings suggest that glycerophospholipid metabolism may serve as potential therapeutic targets and diagnostic biomarkers for ozone-induced pulmonary inflammatory injury.
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spelling doaj-art-c59d82dde0cc45b78d2a6a8597ae2af12025-08-20T03:13:45ZengMDPI AGToxics2305-63042025-04-0113427110.3390/toxics13040271Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and TranscriptomicsXiaolei Zhou0Yunnian Guo1Xiaotong Jian2Xinyi Miao3Pengpeng Wang4Xiaoke Wang5Ling Wang6Huaiyong Chen7Feifei Feng8Department of Respiratory and Critical Care Medicine, Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University, Zhengzhou 450003, ChinaDepartment of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 453001, ChinaDepartment of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 453001, ChinaDepartment of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 453001, ChinaDepartment of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 453001, ChinaDepartment of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226007, ChinaFaculty of Medicine, Macau University of Science and Technology, Macau 999078, ChinaDepartment of Respiratory and Critical Care Medicine, Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University, Zhengzhou 450003, ChinaDepartment of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 453001, ChinaO<sub>3</sub> (ozone) is an environmental pollutant that can exacerbate inflammatory damage and contribute to respiratory diseases. However, the molecular mechanisms and potential targets for intervention in ozone-induced lung inflammatory injury are not yet known. To address this, our study exposed mice to 0.6 ppm and 1.0 ppm of O<sub>3</sub> (3 h/d, 14 d), evaluating lung inflammation through histopathological examinations, lung function assessments, and analyses of white blood cells and inflammatory factors in BALF. Furthermore, we employed transcriptomic and non-targeted metabolomic approaches to decipher differentially expressed genes (DEGs) and metabolites in mouse lung tissue from the 1.0 ppm O<sub>3</sub> exposure group. A comprehensive integration analysis of these omics data was conducted using Pearson correlation analysis. Finally, our findings show that ozone exposure indeed elicits pulmonary inflammation. Transcriptomic analysis identified 311 differentially expressed genes, predominantly implicated in circadian rhythm, IL-17 signaling pathway, and PPAR signaling. Meanwhile, metabolomic profiling revealed 41 differentially regulated metabolites, mainly associated with riboflavin metabolism, glutathione metabolism, and ABC transporter pathways. Integrated multi-omics analysis through Pearson correlation identified three key components (Pla2g10, O-phosphoethanolamine, and phosphorylcholine) showing significant enrichment in glycerophospholipid metabolism. Collectively, our findings suggest that glycerophospholipid metabolism may serve as potential therapeutic targets and diagnostic biomarkers for ozone-induced pulmonary inflammatory injury.https://www.mdpi.com/2305-6304/13/4/271ozonemetabolomicstranscriptomicinflammatory damageglycerophospholipid metabolism
spellingShingle Xiaolei Zhou
Yunnian Guo
Xiaotong Jian
Xinyi Miao
Pengpeng Wang
Xiaoke Wang
Ling Wang
Huaiyong Chen
Feifei Feng
Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics
Toxics
ozone
metabolomics
transcriptomic
inflammatory damage
glycerophospholipid metabolism
title Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics
title_full Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics
title_fullStr Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics
title_full_unstemmed Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics
title_short Revealing the Molecular Mechanisms of Ozone-Induced Pulmonary Inflammatory Injury: Integrated Analysis of Metabolomics and Transcriptomics
title_sort revealing the molecular mechanisms of ozone induced pulmonary inflammatory injury integrated analysis of metabolomics and transcriptomics
topic ozone
metabolomics
transcriptomic
inflammatory damage
glycerophospholipid metabolism
url https://www.mdpi.com/2305-6304/13/4/271
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