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Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction

Pulmonary fibrosis is a progressive disease characterized by epithelial cell damage, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and lung tissue scarring. Melatonin, a hormone produced by the pineal gland, plays an important role in multiple physiological and pathologi...

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Autores principales: Zhang, Lu, Li, Fang, Su, Xiaomin, Li, Yue, Wang, Yining, Fang, Ruonan, Guo, Yingying, Jin, Tongzhu, Shan, Huitong, Zhao, Xiaoguang, Yang, Rui, Shan, Hongli, Liang, Haihai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802616/
https://www.ncbi.nlm.nih.gov/pubmed/31273199
http://dx.doi.org/10.1038/s12276-019-0273-8
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author Zhang, Lu
Li, Fang
Su, Xiaomin
Li, Yue
Wang, Yining
Fang, Ruonan
Guo, Yingying
Jin, Tongzhu
Shan, Huitong
Zhao, Xiaoguang
Yang, Rui
Shan, Hongli
Liang, Haihai
author_facet Zhang, Lu
Li, Fang
Su, Xiaomin
Li, Yue
Wang, Yining
Fang, Ruonan
Guo, Yingying
Jin, Tongzhu
Shan, Huitong
Zhao, Xiaoguang
Yang, Rui
Shan, Hongli
Liang, Haihai
author_sort Zhang, Lu
collection PubMed
description Pulmonary fibrosis is a progressive disease characterized by epithelial cell damage, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and lung tissue scarring. Melatonin, a hormone produced by the pineal gland, plays an important role in multiple physiological and pathological responses in organisms. However, the function of melatonin in the development of bleomycin-induced pulmonary injury is poorly understood. In the present study, we found that melatonin significantly decreased mortality and restored the function of the alveolar epithelium in bleomycin-treated mice. However, pulmonary function mainly depends on type II alveolar epithelial cells (AECIIs) and is linked to mitochondrial integrity. We also found that melatonin reduced the production of reactive oxygen species (ROS) and prevented apoptosis and senescence in AECIIs. Luzindole, a nonselective melatonin receptor antagonist, blocked the protective action of melatonin. Interestingly, we found that the expression of apelin 13 was significantly downregulated in vitro and in vivo and that this downregulation was reversed by melatonin. Furthermore, ML221, an apelin inhibitor, disrupted the beneficial effects of melatonin on alveolar epithelial cells. Taken together, these results suggest that melatonin alleviates lung injury through regulating apelin 13 to improve mitochondrial dysfunction in the process of bleomycin-induced pulmonary injury.
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spelling pubmed-68026162019-10-25 Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction Zhang, Lu Li, Fang Su, Xiaomin Li, Yue Wang, Yining Fang, Ruonan Guo, Yingying Jin, Tongzhu Shan, Huitong Zhao, Xiaoguang Yang, Rui Shan, Hongli Liang, Haihai Exp Mol Med Article Pulmonary fibrosis is a progressive disease characterized by epithelial cell damage, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and lung tissue scarring. Melatonin, a hormone produced by the pineal gland, plays an important role in multiple physiological and pathological responses in organisms. However, the function of melatonin in the development of bleomycin-induced pulmonary injury is poorly understood. In the present study, we found that melatonin significantly decreased mortality and restored the function of the alveolar epithelium in bleomycin-treated mice. However, pulmonary function mainly depends on type II alveolar epithelial cells (AECIIs) and is linked to mitochondrial integrity. We also found that melatonin reduced the production of reactive oxygen species (ROS) and prevented apoptosis and senescence in AECIIs. Luzindole, a nonselective melatonin receptor antagonist, blocked the protective action of melatonin. Interestingly, we found that the expression of apelin 13 was significantly downregulated in vitro and in vivo and that this downregulation was reversed by melatonin. Furthermore, ML221, an apelin inhibitor, disrupted the beneficial effects of melatonin on alveolar epithelial cells. Taken together, these results suggest that melatonin alleviates lung injury through regulating apelin 13 to improve mitochondrial dysfunction in the process of bleomycin-induced pulmonary injury. Nature Publishing Group UK 2019-07-04 /pmc/articles/PMC6802616/ /pubmed/31273199 http://dx.doi.org/10.1038/s12276-019-0273-8 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Lu
Li, Fang
Su, Xiaomin
Li, Yue
Wang, Yining
Fang, Ruonan
Guo, Yingying
Jin, Tongzhu
Shan, Huitong
Zhao, Xiaoguang
Yang, Rui
Shan, Hongli
Liang, Haihai
Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction
title Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction
title_full Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction
title_fullStr Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction
title_full_unstemmed Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction
title_short Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction
title_sort melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802616/
https://www.ncbi.nlm.nih.gov/pubmed/31273199
http://dx.doi.org/10.1038/s12276-019-0273-8
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