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miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis

Silicosis is a very serious occupational disease and it features pathological manifestations of inflammatory infiltration, excessive proliferation of fibroblasts and massive depositions of the extracellular matrix in the lungs. Recent studies described the roles of a variety of microRNAs (miRNAs) in...

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Autores principales: Yuan, Jiali, Li, Ping, Pan, Honghong, Li, Yan, Xu, Qi, Xu, Tiantian, Ji, Xiaoming, Liu, Yi, Yao, Wenxi, Han, Lei, Ni, Chunhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320929/
https://www.ncbi.nlm.nih.gov/pubmed/30467286
http://dx.doi.org/10.3390/ijms19123717
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author Yuan, Jiali
Li, Ping
Pan, Honghong
Li, Yan
Xu, Qi
Xu, Tiantian
Ji, Xiaoming
Liu, Yi
Yao, Wenxi
Han, Lei
Ni, Chunhui
author_facet Yuan, Jiali
Li, Ping
Pan, Honghong
Li, Yan
Xu, Qi
Xu, Tiantian
Ji, Xiaoming
Liu, Yi
Yao, Wenxi
Han, Lei
Ni, Chunhui
author_sort Yuan, Jiali
collection PubMed
description Silicosis is a very serious occupational disease and it features pathological manifestations of inflammatory infiltration, excessive proliferation of fibroblasts and massive depositions of the extracellular matrix in the lungs. Recent studies described the roles of a variety of microRNAs (miRNAs) in fibrotic diseases. Here, we aimed to explore the potential mechanism of miR-542-5p in the activation of lung fibroblasts. To induce a pulmonary fibrosis mouse model, silica suspension and the miR-542-5p agomir were administered to mice by intratracheal instillation and tail vein injection. We found that miR-542-5p was significantly decreased in mouse fibrotic lung tissues and up-regulation of miR-542-5p visually attenuated a series of fibrotic lesions, including alveolar structural damage, alveolar interstitial thickening and silica-induced nodule formation. The down-regulation of miR-542-5p was also observed in mouse fibroblast (NIH-3T3) treated with transforming growth factor β1 (TGF-β1). The proliferation and migration ability of NIH-3T3 cells were also inhibited by the transfection of miR-542-5p mimic. Integrin α6 (Itga6), reported as a cell surface protein associated with fibroblast proliferation, was confirmed to be a direct target of miR-542-5p. The knockdown of Itga6 significantly inhibited the phosphorylation of FAK/PI3K/AKT. In conclusion, miR-542-5p has a potential function for reducing the proliferation of fibroblasts and inhibiting silica-induced pulmonary fibrosis, which might be partially realized by directly binding to Itga6. Our data suggested that miR-542-5p might be a new therapeutic target for silicosis or other pulmonary fibrosis.
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spelling pubmed-63209292019-01-07 miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis Yuan, Jiali Li, Ping Pan, Honghong Li, Yan Xu, Qi Xu, Tiantian Ji, Xiaoming Liu, Yi Yao, Wenxi Han, Lei Ni, Chunhui Int J Mol Sci Article Silicosis is a very serious occupational disease and it features pathological manifestations of inflammatory infiltration, excessive proliferation of fibroblasts and massive depositions of the extracellular matrix in the lungs. Recent studies described the roles of a variety of microRNAs (miRNAs) in fibrotic diseases. Here, we aimed to explore the potential mechanism of miR-542-5p in the activation of lung fibroblasts. To induce a pulmonary fibrosis mouse model, silica suspension and the miR-542-5p agomir were administered to mice by intratracheal instillation and tail vein injection. We found that miR-542-5p was significantly decreased in mouse fibrotic lung tissues and up-regulation of miR-542-5p visually attenuated a series of fibrotic lesions, including alveolar structural damage, alveolar interstitial thickening and silica-induced nodule formation. The down-regulation of miR-542-5p was also observed in mouse fibroblast (NIH-3T3) treated with transforming growth factor β1 (TGF-β1). The proliferation and migration ability of NIH-3T3 cells were also inhibited by the transfection of miR-542-5p mimic. Integrin α6 (Itga6), reported as a cell surface protein associated with fibroblast proliferation, was confirmed to be a direct target of miR-542-5p. The knockdown of Itga6 significantly inhibited the phosphorylation of FAK/PI3K/AKT. In conclusion, miR-542-5p has a potential function for reducing the proliferation of fibroblasts and inhibiting silica-induced pulmonary fibrosis, which might be partially realized by directly binding to Itga6. Our data suggested that miR-542-5p might be a new therapeutic target for silicosis or other pulmonary fibrosis. MDPI 2018-11-22 /pmc/articles/PMC6320929/ /pubmed/30467286 http://dx.doi.org/10.3390/ijms19123717 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yuan, Jiali
Li, Ping
Pan, Honghong
Li, Yan
Xu, Qi
Xu, Tiantian
Ji, Xiaoming
Liu, Yi
Yao, Wenxi
Han, Lei
Ni, Chunhui
miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis
title miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis
title_full miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis
title_fullStr miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis
title_full_unstemmed miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis
title_short miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis
title_sort mir-542-5p attenuates fibroblast activation by targeting integrin α6 in silica-induced pulmonary fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320929/
https://www.ncbi.nlm.nih.gov/pubmed/30467286
http://dx.doi.org/10.3390/ijms19123717
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