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Crucial Role of miR-433 in Regulating Cardiac Fibrosis
Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039681/ https://www.ncbi.nlm.nih.gov/pubmed/27698941 http://dx.doi.org/10.7150/thno.15007 |
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author | Tao, Lichan Bei, Yihua Chen, Ping Lei, Zhiyong Fu, Siyi Zhang, Haifeng Xu, Jiahong Che, Lin Chen, Xiongwen Sluijter, Joost PG Das, Saumya Cretoiu, Dragos Xu, Bin Zhong, Jiuchang Xiao, Junjie Li, Xinli |
author_facet | Tao, Lichan Bei, Yihua Chen, Ping Lei, Zhiyong Fu, Siyi Zhang, Haifeng Xu, Jiahong Che, Lin Chen, Xiongwen Sluijter, Joost PG Das, Saumya Cretoiu, Dragos Xu, Bin Zhong, Jiuchang Xiao, Junjie Li, Xinli |
author_sort | Tao, Lichan |
collection | PubMed |
description | Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis. |
format | Online Article Text |
id | pubmed-5039681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-50396812016-10-03 Crucial Role of miR-433 in Regulating Cardiac Fibrosis Tao, Lichan Bei, Yihua Chen, Ping Lei, Zhiyong Fu, Siyi Zhang, Haifeng Xu, Jiahong Che, Lin Chen, Xiongwen Sluijter, Joost PG Das, Saumya Cretoiu, Dragos Xu, Bin Zhong, Jiuchang Xiao, Junjie Li, Xinli Theranostics Research Paper Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis. Ivyspring International Publisher 2016-09-10 /pmc/articles/PMC5039681/ /pubmed/27698941 http://dx.doi.org/10.7150/thno.15007 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. |
spellingShingle | Research Paper Tao, Lichan Bei, Yihua Chen, Ping Lei, Zhiyong Fu, Siyi Zhang, Haifeng Xu, Jiahong Che, Lin Chen, Xiongwen Sluijter, Joost PG Das, Saumya Cretoiu, Dragos Xu, Bin Zhong, Jiuchang Xiao, Junjie Li, Xinli Crucial Role of miR-433 in Regulating Cardiac Fibrosis |
title | Crucial Role of miR-433 in Regulating Cardiac Fibrosis |
title_full | Crucial Role of miR-433 in Regulating Cardiac Fibrosis |
title_fullStr | Crucial Role of miR-433 in Regulating Cardiac Fibrosis |
title_full_unstemmed | Crucial Role of miR-433 in Regulating Cardiac Fibrosis |
title_short | Crucial Role of miR-433 in Regulating Cardiac Fibrosis |
title_sort | crucial role of mir-433 in regulating cardiac fibrosis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039681/ https://www.ncbi.nlm.nih.gov/pubmed/27698941 http://dx.doi.org/10.7150/thno.15007 |
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