Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion
Abstract Background Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in heal...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12989-023-00534-w |
| _version_ | 1797774398155915264 |
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| author | Qi Liu Jiali Weng Chenfei Li Yi Feng Meiqin Xie Xiaohui Wang Qing Chang Mengnan Li Kian Fan Chung Ian M Adcock Yan Huang Hai Zhang Feng Li |
| author_facet | Qi Liu Jiali Weng Chenfei Li Yi Feng Meiqin Xie Xiaohui Wang Qing Chang Mengnan Li Kian Fan Chung Ian M Adcock Yan Huang Hai Zhang Feng Li |
| author_sort | Qi Liu |
| collection | DOAJ |
| description | Abstract Background Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM2.5-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively. Methods Alveolar epithelial (A549) cells were treated with PM2.5 (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or distilled water for two consecutive days. Results PM2.5 exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM2.5-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM2.5-induced acute lung injury in mice. Conclusion Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM2.5-induced alveolar epithelial cell damage in vitro and lung injury in vivo. |
| first_indexed | 2024-03-12T22:19:29Z |
| format | Article |
| id | doaj.art-1aeb7b06bb9c48e7aec731f5eff6b243 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-03-12T22:19:29Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-1aeb7b06bb9c48e7aec731f5eff6b2432023-07-23T11:04:07ZengBMCParticle and Fibre Toxicology1743-89772023-07-0120111810.1186/s12989-023-00534-wAttenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusionQi Liu0Jiali Weng1Chenfei Li2Yi Feng3Meiqin Xie4Xiaohui Wang5Qing Chang6Mengnan Li7Kian Fan Chung8Ian M Adcock9Yan Huang10Hai Zhang11Feng Li12Department of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineAirway Disease Section, National Heart and Lung Institute, Imperial CollegeAirway Disease Section, National Heart and Lung Institute, Imperial CollegeSchool of Pharmacy, Anhui Medical UniversityDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineDepartment of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of medicineAbstract Background Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM2.5-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively. Methods Alveolar epithelial (A549) cells were treated with PM2.5 (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or distilled water for two consecutive days. Results PM2.5 exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM2.5-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM2.5-induced acute lung injury in mice. Conclusion Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM2.5-induced alveolar epithelial cell damage in vitro and lung injury in vivo.https://doi.org/10.1186/s12989-023-00534-wMitochondrial fissionMitochondrial fusionPM2.5MitophagyMitochondrial oxygen consumption rate (OCR)Mitochondrial morphology |
| spellingShingle | Qi Liu Jiali Weng Chenfei Li Yi Feng Meiqin Xie Xiaohui Wang Qing Chang Mengnan Li Kian Fan Chung Ian M Adcock Yan Huang Hai Zhang Feng Li Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion Particle and Fibre Toxicology Mitochondrial fission Mitochondrial fusion PM2.5 Mitophagy Mitochondrial oxygen consumption rate (OCR) Mitochondrial morphology |
| title | Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
| title_full | Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
| title_fullStr | Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
| title_full_unstemmed | Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
| title_short | Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
| title_sort | attenuation of pm2 5 induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
| topic | Mitochondrial fission Mitochondrial fusion PM2.5 Mitophagy Mitochondrial oxygen consumption rate (OCR) Mitochondrial morphology |
| url | https://doi.org/10.1186/s12989-023-00534-w |
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