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Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice
BACKGROUND: Multi-walled carbon nanotube (MWCNT)-induced lung fibrosis leads to health concerns in human. However, the mechanisms underlying fibrosis pathogenesis remains unclear. The adenosine (ADO) is produced in response to injury and serves a detrimental role in lung fibrosis. In this study, we...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440149/ https://www.ncbi.nlm.nih.gov/pubmed/30922349 http://dx.doi.org/10.1186/s12951-019-0478-y |
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author | Liu, Biying Bing, Qizheng Li, Siyu Han, Bing Lu, Jingjing Baiyun, Ruiqi Zhang, Xiaoya Lv, Yueying Wu, Hao Zhang, Zhigang |
author_facet | Liu, Biying Bing, Qizheng Li, Siyu Han, Bing Lu, Jingjing Baiyun, Ruiqi Zhang, Xiaoya Lv, Yueying Wu, Hao Zhang, Zhigang |
author_sort | Liu, Biying |
collection | PubMed |
description | BACKGROUND: Multi-walled carbon nanotube (MWCNT)-induced lung fibrosis leads to health concerns in human. However, the mechanisms underlying fibrosis pathogenesis remains unclear. The adenosine (ADO) is produced in response to injury and serves a detrimental role in lung fibrosis. In this study, we aimed to explore the ADO signaling in the progression of lung fibrosis induced by MWCNT. RESULTS: MWCNT exposure markedly increased A(2B) adenosine receptor (A(2B)AR) expression in the lungs and ADO level in bronchoalveolar lavage fluid, combined with elevation of blood neutrophils, collagen fiber deposition, and activation of myeloperoxidase (MPO) activity in the lungs. Furthermore, MWCNT exposure elicited an activation of transforming growth factor (TGF)-β1 and follistatin-like 1 (Fstl1), leading to fibroblasts recruitment and differentiation into myofibroblasts in the lungs in an A(2B)AR-dependent manner. Conversely, treatment of the selective A(2B)AR antagonist CVT-6883 exhibited a significant reduction in levels of fibrosis mediators and efficiently decreased cytotoxicity and inflammatory in MWCNT treated mice. CONCLUSION: Our results reveal that accumulation of extracellular ADO promotes the process of the fibroblast-to-myofibroblast transition via A(2B)AR/TGF-β1/Fstl1 signaling in MWCNT-induced lung fibrosis. |
format | Online Article Text |
id | pubmed-6440149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64401492019-04-11 Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice Liu, Biying Bing, Qizheng Li, Siyu Han, Bing Lu, Jingjing Baiyun, Ruiqi Zhang, Xiaoya Lv, Yueying Wu, Hao Zhang, Zhigang J Nanobiotechnology Research BACKGROUND: Multi-walled carbon nanotube (MWCNT)-induced lung fibrosis leads to health concerns in human. However, the mechanisms underlying fibrosis pathogenesis remains unclear. The adenosine (ADO) is produced in response to injury and serves a detrimental role in lung fibrosis. In this study, we aimed to explore the ADO signaling in the progression of lung fibrosis induced by MWCNT. RESULTS: MWCNT exposure markedly increased A(2B) adenosine receptor (A(2B)AR) expression in the lungs and ADO level in bronchoalveolar lavage fluid, combined with elevation of blood neutrophils, collagen fiber deposition, and activation of myeloperoxidase (MPO) activity in the lungs. Furthermore, MWCNT exposure elicited an activation of transforming growth factor (TGF)-β1 and follistatin-like 1 (Fstl1), leading to fibroblasts recruitment and differentiation into myofibroblasts in the lungs in an A(2B)AR-dependent manner. Conversely, treatment of the selective A(2B)AR antagonist CVT-6883 exhibited a significant reduction in levels of fibrosis mediators and efficiently decreased cytotoxicity and inflammatory in MWCNT treated mice. CONCLUSION: Our results reveal that accumulation of extracellular ADO promotes the process of the fibroblast-to-myofibroblast transition via A(2B)AR/TGF-β1/Fstl1 signaling in MWCNT-induced lung fibrosis. BioMed Central 2019-03-29 /pmc/articles/PMC6440149/ /pubmed/30922349 http://dx.doi.org/10.1186/s12951-019-0478-y Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Liu, Biying Bing, Qizheng Li, Siyu Han, Bing Lu, Jingjing Baiyun, Ruiqi Zhang, Xiaoya Lv, Yueying Wu, Hao Zhang, Zhigang Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice |
title | Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice |
title_full | Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice |
title_fullStr | Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice |
title_full_unstemmed | Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice |
title_short | Role of A(2B) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice |
title_sort | role of a(2b) adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440149/ https://www.ncbi.nlm.nih.gov/pubmed/30922349 http://dx.doi.org/10.1186/s12951-019-0478-y |
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