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Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice
Recent studies have begun to reveal critical roles of microRNAs (miRNAs) in the pathogenesis of cardiac hypertrophy and dysfunction. In this study, we tested whether a transforming growth factor-β (TGF-β)-regulated miRNA played a pivotal role in the development of cardiac hypertrophy and heart failu...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292295/ https://www.ncbi.nlm.nih.gov/pubmed/21844895 http://dx.doi.org/10.1038/cr.2011.132 |
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author | Wang, Jian Song, Yao Zhang, Yan Xiao, Han Sun, Qiang Hou, Ning Guo, Shuilong Wang, Youliang Fan, Kaiji Zhan, Dawei Zha, Lagabaiyila Cao, Yang Li, Zhenhua Cheng, Xuan Zhang, Youyi Yang, Xiao |
author_facet | Wang, Jian Song, Yao Zhang, Yan Xiao, Han Sun, Qiang Hou, Ning Guo, Shuilong Wang, Youliang Fan, Kaiji Zhan, Dawei Zha, Lagabaiyila Cao, Yang Li, Zhenhua Cheng, Xuan Zhang, Youyi Yang, Xiao |
author_sort | Wang, Jian |
collection | PubMed |
description | Recent studies have begun to reveal critical roles of microRNAs (miRNAs) in the pathogenesis of cardiac hypertrophy and dysfunction. In this study, we tested whether a transforming growth factor-β (TGF-β)-regulated miRNA played a pivotal role in the development of cardiac hypertrophy and heart failure (HF). We observed that miR-27b was upregulated in hearts of cardiomyocyte-specific Smad4 knockout mice, which developed cardiac hypertrophy. In vitro experiments showed that the miR-27b expression could be inhibited by TGF-β1 and that its overexpression promoted hypertrophic cell growth, while the miR-27b suppression led to inhibition of the hypertrophic cell growth caused by phenylephrine (PE) treatment. Furthermore, the analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-27b revealed that miR-27b overexpression was sufficient to induce cardiac hypertrophy and dysfunction. We validated the peroxisome proliferator-activated receptor-γ (PPAR-γ) as a direct target of miR-27b in cardiomyocyte. Consistently, the miR-27b transgenic mice displayed significantly lower levels of PPAR-γ than the control mice. Furthermore, in vivo silencing of miR-27b using a specific antagomir in a pressure-overload-induced mouse model of HF increased cardiac PPAR-γ expression, attenuated cardiac hypertrophy and dysfunction. The results of our study demonstrate that TGF-β1-regulated miR-27b is involved in the regulation of cardiac hypertrophy, and validate miR-27b as an efficient therapeutic target for cardiac diseases. |
format | Online Article Text |
id | pubmed-3292295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-32922952012-03-02 Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice Wang, Jian Song, Yao Zhang, Yan Xiao, Han Sun, Qiang Hou, Ning Guo, Shuilong Wang, Youliang Fan, Kaiji Zhan, Dawei Zha, Lagabaiyila Cao, Yang Li, Zhenhua Cheng, Xuan Zhang, Youyi Yang, Xiao Cell Res Original Article Recent studies have begun to reveal critical roles of microRNAs (miRNAs) in the pathogenesis of cardiac hypertrophy and dysfunction. In this study, we tested whether a transforming growth factor-β (TGF-β)-regulated miRNA played a pivotal role in the development of cardiac hypertrophy and heart failure (HF). We observed that miR-27b was upregulated in hearts of cardiomyocyte-specific Smad4 knockout mice, which developed cardiac hypertrophy. In vitro experiments showed that the miR-27b expression could be inhibited by TGF-β1 and that its overexpression promoted hypertrophic cell growth, while the miR-27b suppression led to inhibition of the hypertrophic cell growth caused by phenylephrine (PE) treatment. Furthermore, the analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-27b revealed that miR-27b overexpression was sufficient to induce cardiac hypertrophy and dysfunction. We validated the peroxisome proliferator-activated receptor-γ (PPAR-γ) as a direct target of miR-27b in cardiomyocyte. Consistently, the miR-27b transgenic mice displayed significantly lower levels of PPAR-γ than the control mice. Furthermore, in vivo silencing of miR-27b using a specific antagomir in a pressure-overload-induced mouse model of HF increased cardiac PPAR-γ expression, attenuated cardiac hypertrophy and dysfunction. The results of our study demonstrate that TGF-β1-regulated miR-27b is involved in the regulation of cardiac hypertrophy, and validate miR-27b as an efficient therapeutic target for cardiac diseases. Nature Publishing Group 2012-03 2011-08-16 /pmc/articles/PMC3292295/ /pubmed/21844895 http://dx.doi.org/10.1038/cr.2011.132 Text en Copyright © 2012 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences http://creativecommons.org/licenses/by-nc-nd/3.0 This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0 |
spellingShingle | Original Article Wang, Jian Song, Yao Zhang, Yan Xiao, Han Sun, Qiang Hou, Ning Guo, Shuilong Wang, Youliang Fan, Kaiji Zhan, Dawei Zha, Lagabaiyila Cao, Yang Li, Zhenhua Cheng, Xuan Zhang, Youyi Yang, Xiao Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice |
title | Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice |
title_full | Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice |
title_fullStr | Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice |
title_full_unstemmed | Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice |
title_short | Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice |
title_sort | cardiomyocyte overexpression of mir-27b induces cardiac hypertrophy and dysfunction in mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292295/ https://www.ncbi.nlm.nih.gov/pubmed/21844895 http://dx.doi.org/10.1038/cr.2011.132 |
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