The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis

To identify microRNAs (miRNAs, miRs) with potential roles in lung fibrogenesis, we performed genome-wide profiling of miRNA expression in lung tissues from a silica-induced mouse model of pulmonary fibrosis using microarrays. Seventeen miRNAs were selected for validation via qRT-PCR based on the fol...

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Main Authors: Ji, Xiaoming, Wu, Baiqun, Fan, Jingjing, Han, Ruhui, Luo, Chen, Wang, Ting, Yang, Jingjin, Han, Lei, Zhu, Baoli, Wei, Dong, Chen, Jingyu, Ni, Chunhui
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569899/
id pubmed-4569899
recordtype oai_dc
spelling pubmed-45698992015-09-28 The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis Ji, Xiaoming Wu, Baiqun Fan, Jingjing Han, Ruhui Luo, Chen Wang, Ting Yang, Jingjin Han, Lei Zhu, Baoli Wei, Dong Chen, Jingyu Ni, Chunhui Article To identify microRNAs (miRNAs, miRs) with potential roles in lung fibrogenesis, we performed genome-wide profiling of miRNA expression in lung tissues from a silica-induced mouse model of pulmonary fibrosis using microarrays. Seventeen miRNAs were selected for validation via qRT-PCR based on the fold changes between the silica and the control group. The dysregulation of five miRNAs, including miR-21, miR-455, miR-151-3p, miR-486-5p and miR-3107, were confirmed by qRT-PCRs in silica-induced mouse model of pulmonary fibrosis and were also confirmed in a bleomycin (BLM)-induced mouse lung fibrosis. Notably, miR-486-5p levels were decreased in the serum samples of patients with silicosis, as well as in the lung tissues of patients with silicosis and idiopathic pulmonary fibrosis (IPF). In addition, as determined by luciferase assays and Western blotting, SMAD2, a crucial mediator of pulmonary fibrosis, was identified to be one of target genes of miR-486-5p. To test the potential therapeutic significance of this miRNA, we overexpressed miR-486-5p in animal models. At day 28, miR-486-5p expression significantly decreased both the distribution and severity of lung lesions compared with the silica group (P < 0.01). In addition, miR-486-5p had a similar effect in the BLM group (P < 0.001). These results indicate that miR-486-5p may inhibit fibrosis. Nature Publishing Group 2015-09-15 /pmc/articles/PMC4569899/ /pubmed/26370615 http://dx.doi.org/10.1038/srep14131 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ji, Xiaoming
Wu, Baiqun
Fan, Jingjing
Han, Ruhui
Luo, Chen
Wang, Ting
Yang, Jingjin
Han, Lei
Zhu, Baoli
Wei, Dong
Chen, Jingyu
Ni, Chunhui
spellingShingle Ji, Xiaoming
Wu, Baiqun
Fan, Jingjing
Han, Ruhui
Luo, Chen
Wang, Ting
Yang, Jingjin
Han, Lei
Zhu, Baoli
Wei, Dong
Chen, Jingyu
Ni, Chunhui
The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis
author_facet Ji, Xiaoming
Wu, Baiqun
Fan, Jingjing
Han, Ruhui
Luo, Chen
Wang, Ting
Yang, Jingjin
Han, Lei
Zhu, Baoli
Wei, Dong
Chen, Jingyu
Ni, Chunhui
author_sort Ji, Xiaoming
title The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis
title_short The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis
title_full The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis
title_fullStr The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis
title_full_unstemmed The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis
title_sort anti-fibrotic effects and mechanisms of microrna-486-5p in pulmonary fibrosis
description To identify microRNAs (miRNAs, miRs) with potential roles in lung fibrogenesis, we performed genome-wide profiling of miRNA expression in lung tissues from a silica-induced mouse model of pulmonary fibrosis using microarrays. Seventeen miRNAs were selected for validation via qRT-PCR based on the fold changes between the silica and the control group. The dysregulation of five miRNAs, including miR-21, miR-455, miR-151-3p, miR-486-5p and miR-3107, were confirmed by qRT-PCRs in silica-induced mouse model of pulmonary fibrosis and were also confirmed in a bleomycin (BLM)-induced mouse lung fibrosis. Notably, miR-486-5p levels were decreased in the serum samples of patients with silicosis, as well as in the lung tissues of patients with silicosis and idiopathic pulmonary fibrosis (IPF). In addition, as determined by luciferase assays and Western blotting, SMAD2, a crucial mediator of pulmonary fibrosis, was identified to be one of target genes of miR-486-5p. To test the potential therapeutic significance of this miRNA, we overexpressed miR-486-5p in animal models. At day 28, miR-486-5p expression significantly decreased both the distribution and severity of lung lesions compared with the silica group (P < 0.01). In addition, miR-486-5p had a similar effect in the BLM group (P < 0.001). These results indicate that miR-486-5p may inhibit fibrosis.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569899/
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