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Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion
BACKGROUND: Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM(2.5)) 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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353144/ https://www.ncbi.nlm.nih.gov/pubmed/37464447 http://dx.doi.org/10.1186/s12989-023-00534-w |
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author | Liu, Qi Weng, Jiali Li, Chenfei Feng, Yi Xie, Meiqin Wang, Xiaohui Chang, Qing Li, Mengnan Chung, Kian Fan Adcock, Ian M Huang, Yan Zhang, Hai Li, Feng |
author_facet | Liu, Qi Weng, Jiali Li, Chenfei Feng, Yi Xie, Meiqin Wang, Xiaohui Chang, Qing Li, Mengnan Chung, Kian Fan Adcock, Ian M Huang, Yan Zhang, Hai Li, Feng |
author_sort | Liu, Qi |
collection | PubMed |
description | BACKGROUND: Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM(2.5)) 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 PM(2.5)-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 PM(2.5) (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 PM(2.5) (7.8 mg/kg) or distilled water for two consecutive days. RESULTS: PM(2.5) 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 PM(2.5)-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM(2.5)-induced acute lung injury in mice. CONCLUSION: Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM(2.5)-induced alveolar epithelial cell damage in vitro and lung injury in vivo. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-023-00534-w. |
format | Online Article Text |
id | pubmed-10353144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103531442023-07-19 Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion Liu, Qi Weng, Jiali Li, Chenfei Feng, Yi Xie, Meiqin Wang, Xiaohui Chang, Qing Li, Mengnan Chung, Kian Fan Adcock, Ian M Huang, Yan Zhang, Hai Li, Feng Part Fibre Toxicol Research BACKGROUND: Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM(2.5)) 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 PM(2.5)-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 PM(2.5) (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 PM(2.5) (7.8 mg/kg) or distilled water for two consecutive days. RESULTS: PM(2.5) 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 PM(2.5)-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM(2.5)-induced acute lung injury in mice. CONCLUSION: Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM(2.5)-induced alveolar epithelial cell damage in vitro and lung injury in vivo. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-023-00534-w. BioMed Central 2023-07-18 /pmc/articles/PMC10353144/ /pubmed/37464447 http://dx.doi.org/10.1186/s12989-023-00534-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Liu, Qi Weng, Jiali Li, Chenfei Feng, Yi Xie, Meiqin Wang, Xiaohui Chang, Qing Li, Mengnan Chung, Kian Fan Adcock, Ian M Huang, Yan Zhang, Hai Li, Feng Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
title | Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
title_full | Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
title_fullStr | Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
title_full_unstemmed | Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
title_short | Attenuation of PM(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
title_sort | attenuation of pm(2.5)-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353144/ https://www.ncbi.nlm.nih.gov/pubmed/37464447 http://dx.doi.org/10.1186/s12989-023-00534-w |
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