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Int. J. Mol. Sci. 2017, 18(11), 2357; https://doi.org/10.3390/ijms18112357

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

1
School of Public Health, Xuzhou Medical University, Xuzhou 221004, China
2
Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 7 September 2017 / Revised: 1 November 2017 / Accepted: 3 November 2017 / Published: 7 November 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: pulmonary fibrosis; silicosis; miR-1224-5p; BECN1; mitophagy pulmonary fibrosis; silicosis; miR-1224-5p; BECN1; mitophagy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wu, Q.; Xu, T.; Liu, Y.; Li, Y.; Yuan, J.; Yao, W.; Xu, Q.; Yan, W.; Ni, C. miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1. Int. J. Mol. Sci. 2017, 18, 2357.

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