Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783283398798737408 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5713326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wuqiuyun mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT xutiantian mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT liuyi mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT liyan mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT yuanjiali mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT yaowenxi mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT xuqi mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT yanweiwen mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 AT nichunhui mir12245pmediatesmitochondrialdamagetoaffectsilicainducedpulmonaryfibrosisbytargetingbecn1 |