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miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1

Silicosis is associated with fibroblast proliferation and extracellular matrix deposition in lung tissues. The dysregulation of miR-1224-5p has been implicated in several human cancers; however, the expression and function of miR-1224-5p in silicosis is unknown. The mitochondrial dysfunctions play c...

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Autores principales: Wu, Qiuyun, Xu, Tiantian, Liu, Yi, Li, Yan, Yuan, Jiali, Yao, Wenxi, Xu, Qi, Yan, Weiwen, Ni, Chunhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713326/
https://www.ncbi.nlm.nih.gov/pubmed/29112159
http://dx.doi.org/10.3390/ijms18112357
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author Wu, Qiuyun
Xu, Tiantian
Liu, Yi
Li, Yan
Yuan, Jiali
Yao, Wenxi
Xu, Qi
Yan, Weiwen
Ni, Chunhui
author_facet Wu, Qiuyun
Xu, Tiantian
Liu, Yi
Li, Yan
Yuan, Jiali
Yao, Wenxi
Xu, Qi
Yan, Weiwen
Ni, Chunhui
author_sort Wu, Qiuyun
collection PubMed
description Silicosis is associated with fibroblast proliferation and extracellular matrix deposition in lung tissues. The dysregulation of miR-1224-5p has been implicated in several human cancers; however, the expression and function of miR-1224-5p in silicosis is unknown. The mitochondrial dysfunctions play critical roles in some diseases, but how these processes are regulated in silicosis remains limited. Here, we explored the role of miR-1224-5p in a mouse model of silicosis. We showed that the expression of miR-1224-5p is increased both in lung tissues of silica-induced pulmonary fibrosis and fibroblasts exposed to TGF-β1. Repression of miR-1224-5p expression attenuated silica-induced fibrotic progression in vivo and TGF-β1-induced myofibroblast differentiation in vitro. Additionally, we demonstrated that miR-1224-5p facilitated silica-induced pulmonary fibrosis primarily by repressing one of target genes, BECN1, thereby blocking PARK2 translocation to mitochondria and inducing the accumulation of damaged mitochondria. Furthermore, the activation of PDGFR signal mediated by mitochondrial damage and insufficient mitophagy resulted in myofibroblast differentiation. Collectively, these data indicated that miR-1224-5p exerts key functions in silica-induced pulmonary fibrosis and may represent a potential therapeutic target for silicosis.
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spelling pubmed-57133262017-12-07 miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1 Wu, Qiuyun Xu, Tiantian Liu, Yi Li, Yan Yuan, Jiali Yao, Wenxi Xu, Qi Yan, Weiwen Ni, Chunhui Int J Mol Sci Article Silicosis is associated with fibroblast proliferation and extracellular matrix deposition in lung tissues. The dysregulation of miR-1224-5p has been implicated in several human cancers; however, the expression and function of miR-1224-5p in silicosis is unknown. The mitochondrial dysfunctions play critical roles in some diseases, but how these processes are regulated in silicosis remains limited. Here, we explored the role of miR-1224-5p in a mouse model of silicosis. We showed that the expression of miR-1224-5p is increased both in lung tissues of silica-induced pulmonary fibrosis and fibroblasts exposed to TGF-β1. Repression of miR-1224-5p expression attenuated silica-induced fibrotic progression in vivo and TGF-β1-induced myofibroblast differentiation in vitro. Additionally, we demonstrated that miR-1224-5p facilitated silica-induced pulmonary fibrosis primarily by repressing one of target genes, BECN1, thereby blocking PARK2 translocation to mitochondria and inducing the accumulation of damaged mitochondria. Furthermore, the activation of PDGFR signal mediated by mitochondrial damage and insufficient mitophagy resulted in myofibroblast differentiation. Collectively, these data indicated that miR-1224-5p exerts key functions in silica-induced pulmonary fibrosis and may represent a potential therapeutic target for silicosis. MDPI 2017-11-07 /pmc/articles/PMC5713326/ /pubmed/29112159 http://dx.doi.org/10.3390/ijms18112357 Text en © 2017 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
Wu, Qiuyun
Xu, Tiantian
Liu, Yi
Li, Yan
Yuan, Jiali
Yao, Wenxi
Xu, Qi
Yan, Weiwen
Ni, Chunhui
miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1
title miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1
title_full miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1
title_fullStr miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1
title_full_unstemmed miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1
title_short miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1
title_sort mir-1224-5p mediates mitochondrial damage to affect silica-induced pulmonary fibrosis by targeting becn1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713326/
https://www.ncbi.nlm.nih.gov/pubmed/29112159
http://dx.doi.org/10.3390/ijms18112357
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