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Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition
Silicosis is a devastating occupational disease caused by long‐term inhalation of silica particles, inducing irreversible lung damage and affecting lung function, without effective treatment. Mesenchymal stem cells (MSCs) are a heterogeneous subset of adult stem cells that exhibit excellent self‐ren...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256359/ https://www.ncbi.nlm.nih.gov/pubmed/34076355 http://dx.doi.org/10.1111/jcmm.16621 |
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author | Wei, Jingjing Zhao, Qiuyan Yang, Guo Huang, Ruoxuan Li, Chao Qi, Yuanmeng Hao, Changfu Yao, Wu |
author_facet | Wei, Jingjing Zhao, Qiuyan Yang, Guo Huang, Ruoxuan Li, Chao Qi, Yuanmeng Hao, Changfu Yao, Wu |
author_sort | Wei, Jingjing |
collection | PubMed |
description | Silicosis is a devastating occupational disease caused by long‐term inhalation of silica particles, inducing irreversible lung damage and affecting lung function, without effective treatment. Mesenchymal stem cells (MSCs) are a heterogeneous subset of adult stem cells that exhibit excellent self‐renewal capacity, multi‐lineage differentiation potential and immunomodulatory properties. The aim of this study was to explore the effect of bone marrow‐derived mesenchymal stem cells (BMSCs) in a silica‐induced rat model of pulmonary fibrosis. The rats were treated with BMSCs on days 14, 28 and 42 after perfusion with silica. Histological examination and hydroxyproline assays showed that BMSCs alleviated silica‐induced pulmonary fibrosis in rats. Results from ELISA and qRT‐PCR indicated that BMSCs inhibited the expression of inflammatory cytokines TNF‐α, IL‐1β and IL‐6 in lung tissues and bronchoalveolar lavage fluid of rats exposed to silica particles. We also performed qRT‐PCR, Western blot and immunohistochemistry to examine epithelial‐mesenchymal transition (EMT)–related indicators and demonstrated that BMSCs up‐regulate E‐cadherin and down‐regulate vimentin and extracellular matrix (ECM) components such as fibronectin and collagen Ⅰ. Additionally, BMSCs inhibited the silica‐induced increase in TGF‐β1, p‐Smad2 and p‐Smad3 and decrease in Smad7. These results suggested that BMSCs can inhibit inflammation and reverse EMT through the inhibition of the TGF‐β/Smad signalling pathway to exhibit an anti‐fibrotic effect in the rat silicosis model. Our study provides a new and meaningful perspective for silicosis treatment strategies. |
format | Online Article Text |
id | pubmed-8256359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82563592021-07-12 Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition Wei, Jingjing Zhao, Qiuyan Yang, Guo Huang, Ruoxuan Li, Chao Qi, Yuanmeng Hao, Changfu Yao, Wu J Cell Mol Med Original Articles Silicosis is a devastating occupational disease caused by long‐term inhalation of silica particles, inducing irreversible lung damage and affecting lung function, without effective treatment. Mesenchymal stem cells (MSCs) are a heterogeneous subset of adult stem cells that exhibit excellent self‐renewal capacity, multi‐lineage differentiation potential and immunomodulatory properties. The aim of this study was to explore the effect of bone marrow‐derived mesenchymal stem cells (BMSCs) in a silica‐induced rat model of pulmonary fibrosis. The rats were treated with BMSCs on days 14, 28 and 42 after perfusion with silica. Histological examination and hydroxyproline assays showed that BMSCs alleviated silica‐induced pulmonary fibrosis in rats. Results from ELISA and qRT‐PCR indicated that BMSCs inhibited the expression of inflammatory cytokines TNF‐α, IL‐1β and IL‐6 in lung tissues and bronchoalveolar lavage fluid of rats exposed to silica particles. We also performed qRT‐PCR, Western blot and immunohistochemistry to examine epithelial‐mesenchymal transition (EMT)–related indicators and demonstrated that BMSCs up‐regulate E‐cadherin and down‐regulate vimentin and extracellular matrix (ECM) components such as fibronectin and collagen Ⅰ. Additionally, BMSCs inhibited the silica‐induced increase in TGF‐β1, p‐Smad2 and p‐Smad3 and decrease in Smad7. These results suggested that BMSCs can inhibit inflammation and reverse EMT through the inhibition of the TGF‐β/Smad signalling pathway to exhibit an anti‐fibrotic effect in the rat silicosis model. Our study provides a new and meaningful perspective for silicosis treatment strategies. John Wiley and Sons Inc. 2021-06-02 2021-07 /pmc/articles/PMC8256359/ /pubmed/34076355 http://dx.doi.org/10.1111/jcmm.16621 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wei, Jingjing Zhao, Qiuyan Yang, Guo Huang, Ruoxuan Li, Chao Qi, Yuanmeng Hao, Changfu Yao, Wu Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition |
title | Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition |
title_full | Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition |
title_fullStr | Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition |
title_full_unstemmed | Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition |
title_short | Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition |
title_sort | mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256359/ https://www.ncbi.nlm.nih.gov/pubmed/34076355 http://dx.doi.org/10.1111/jcmm.16621 |
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