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学科主题: 临床医学
题名:
Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice
作者: Wang, Jian1; Song, Yao2,3; Zhang, Yan1; Xiao, Han2,3; Sun, Qiang1; Hou, Ning1; Guo, Shuilong1; Wang, Youliang1; Fan, Kaiji1; Zhan, Dawei4; Zha, Lagabaiyila1; Cao, Yang1; Li, Zhenhua1; Cheng, Xuan1; Zhang, Youyi2,3; Yang, Xiao1,5
关键词: microRNA ; cardiac hypertrophy ; PPAR-gamma ; transgenic mouse ; therapeutic target
刊名: CELL RESEARCH
发表日期: 2012-03-01
DOI: 10.1038/cr.2011.132
卷: 22, 期:3, 页:516-527
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: ACTIVATED-RECEPTOR-GAMMA ; GROWTH-FACTOR-BETA ; HEART-FAILURE ; MICRORNAS ; PROTEIN ; MYOCARDIUM ; MOUSE ; DIFFERENTIATION ; KNOCKOUT ; DELETION
英文摘要:

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-beta (TGF-beta)-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-beta 1 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-gamma (PPAR-gamma) as a direct target of miR-27b in cardiomyocyte. Consistently, the miR-27b transgenic mice displayed significantly lower levels of PPAR-gamma 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-gamma expression, attenuated cardiac hypertrophy and dysfunction. The results of our study demonstrate that TGF-beta 1-regulated miR-27b is involved in the regulation of cardiac hypertrophy, and validate miR-27b as an efficient therapeutic target for cardiac diseases.

语种: 英语
所属项目编号: 2009ZX09501-027 ; 2011CB504200 ; 31030040 ; 30700424 ; 30871364 ; 31071992 ; 81030001 ; 30971161
项目资助者: Chinese Key Program for Drug Invention ; Chinese National Key Program on Basic Research ; National Natural Science Foundation of China
WOS记录号: WOS:000300942400009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62208
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Inst Biotechnol, State Key Lab Prote, Genet Lab Dev & Dis, Beijing 100071, Peoples R China
2.Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100191, Peoples R China
3.Minist Hlth, Minist Educ, Key Lab Mol Cardiovasc Sci, Key Lab Cardiovasc Mol Biol & Regulatory Pept, Beijing 100191, Peoples R China
4.Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Beijing 100048, Peoples R China
5.Shanghai Jiao Tong Univ, E Inst Shanghai Univ, Model Organism Div, Shanghai 200240, Peoples R China

Recommended Citation:
Wang, Jian,Song, Yao,Zhang, Yan,et al. Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice[J]. CELL RESEARCH,2012,22(3):516-527.
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