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MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis

Inhalation and deposition of crystalline silica particles in the lung can cause pulmonary fibrosis, then leading to silicosis. Given the paucity of effective drugs for silicosis, new insights for understanding the mechanisms of silicosis, including lung fibroblast activation and myofibroblast differ...

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Detalles Bibliográficos
Autores principales: Wu, Qiuyun, Han, Lei, Gui, Wenwen, Wang, Feng, Yan, Weiwen, Jiang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754009/
https://www.ncbi.nlm.nih.gov/pubmed/33135394
http://dx.doi.org/10.1111/jcmm.16051
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author Wu, Qiuyun
Han, Lei
Gui, Wenwen
Wang, Feng
Yan, Weiwen
Jiang, Hua
author_facet Wu, Qiuyun
Han, Lei
Gui, Wenwen
Wang, Feng
Yan, Weiwen
Jiang, Hua
author_sort Wu, Qiuyun
collection PubMed
description Inhalation and deposition of crystalline silica particles in the lung can cause pulmonary fibrosis, then leading to silicosis. Given the paucity of effective drugs for silicosis, new insights for understanding the mechanisms of silicosis, including lung fibroblast activation and myofibroblast differentiation, are essential to explore therapeutic strategies. Our previous research showed that the up‐regulation of miR‐503 alleviated silica‐induced pulmonary fibrosis in mice. In this study, we investigated whether miR‐503 can regulate the TGF‐β1‐induced effects in lung fibroblasts. Mimic‐based strategies aiming at up‐regulating miR‐503 were used to discuss the function of miR‐503 in vivo and in vitro. We found that the expression level of miR‐503 was decreased in fibroblasts stimulated by TGF‐β1, and the up‐regulation of miR‐503 reduced the release of fibrotic factors and inhibited the migration and invasion abilities of fibroblasts. Combined with the up‐regulation of miR‐503 in a mouse model of silica‐induced pulmonary fibrosis, we revealed that miR‐503 mitigated the TGF‐β1‐induced effects in fibroblasts by regulating VEGFA and FGFR1 and then affecting the MAPK/ERK signalling pathway. In conclusion, miR‐503 exerted protective roles in silica‐induced pulmonary fibrosis and may represent a novel and potent candidate for therapeutic strategies in silicosis.
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spelling pubmed-77540092020-12-23 MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis Wu, Qiuyun Han, Lei Gui, Wenwen Wang, Feng Yan, Weiwen Jiang, Hua J Cell Mol Med Original Articles Inhalation and deposition of crystalline silica particles in the lung can cause pulmonary fibrosis, then leading to silicosis. Given the paucity of effective drugs for silicosis, new insights for understanding the mechanisms of silicosis, including lung fibroblast activation and myofibroblast differentiation, are essential to explore therapeutic strategies. Our previous research showed that the up‐regulation of miR‐503 alleviated silica‐induced pulmonary fibrosis in mice. In this study, we investigated whether miR‐503 can regulate the TGF‐β1‐induced effects in lung fibroblasts. Mimic‐based strategies aiming at up‐regulating miR‐503 were used to discuss the function of miR‐503 in vivo and in vitro. We found that the expression level of miR‐503 was decreased in fibroblasts stimulated by TGF‐β1, and the up‐regulation of miR‐503 reduced the release of fibrotic factors and inhibited the migration and invasion abilities of fibroblasts. Combined with the up‐regulation of miR‐503 in a mouse model of silica‐induced pulmonary fibrosis, we revealed that miR‐503 mitigated the TGF‐β1‐induced effects in fibroblasts by regulating VEGFA and FGFR1 and then affecting the MAPK/ERK signalling pathway. In conclusion, miR‐503 exerted protective roles in silica‐induced pulmonary fibrosis and may represent a novel and potent candidate for therapeutic strategies in silicosis. John Wiley and Sons Inc. 2020-11-01 2020-12 /pmc/articles/PMC7754009/ /pubmed/33135394 http://dx.doi.org/10.1111/jcmm.16051 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://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
Wu, Qiuyun
Han, Lei
Gui, Wenwen
Wang, Feng
Yan, Weiwen
Jiang, Hua
MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis
title MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis
title_full MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis
title_fullStr MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis
title_full_unstemmed MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis
title_short MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis
title_sort mir‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting vegfa and fgfr1 in silica‐induced pulmonary fibrosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754009/
https://www.ncbi.nlm.nih.gov/pubmed/33135394
http://dx.doi.org/10.1111/jcmm.16051
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