MicroRNA-150 Protects Against Pressure Overload-Induced Cardiac Hypertrophy
MicroRNA-150 Protects Against Pressure Overload-Induced Cardiac Hypertrophy
复制标题
DOI：
10.1002/jcb.25057
复制
发表时间：
2015-10-01
影响因子：
4
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Liu, Wanli;Liu, Yu;Huang, He
心脏肥大是心脏对各种肥大刺激的反应;这种情况会发展为心力衰竭和猝死。microRNA（miRs）是一类介导转录后基因沉默的非编码小RNA家族。最近的研究已经确定miR是心脏肥大的重要调节因子。据报道，一种特异性miR，miR-150在肥大小鼠心脏中下调。然而，miR-150作为心脏肥大的调节剂的作用仍不清楚。在本研究中，我们使用功能获得和功能丧失的方法来研究miR-150在主动脉缩窄诱导的心脏肥大中的功能作用。心脏肥大的程度通过超声心动图和心脏样本的病理学和分子分析来评估。我们的研究结果表明，在心脏中过表达miR-150的转基因小鼠通过下调血清反应因子（SRF）来抵抗心脏肥大和纤维化。相反，通过基因敲减或miR-150方法使miR-150功能丧失产生相反的效果。这些研究表明，miR-150在心肌肥厚的调控中起重要作用，SRF参与了miR-150介导的抗心肌肥厚作用。因此，miR-150可能成为心肌肥大的一个新的治疗靶点。J.细胞。116：2166-2176，2015. (c)2015年威利期刊公司
Cardiac hypertrophy is the response of the heart to a variety of hypertrophic stimuli; this condition progresses to heart failure and sudden death. MicroRNAs (miRs) are a family of small, non-coding RNAs that mediate posttranscriptional gene silencing. Recent studies have identified miRs as important regulators in cardiac hypertrophy. One specific miR, miR-150 has been reported to be downregulated in hypertrophic murine hearts. However, the role of miR-150 as a regulator of cardiac hypertrophy remains unclear. In the present study, we used gain-of-function and loss-of-function approaches to investigate the functional roles of miR-150 in cardiac hypertrophy induced by aortic banding. The extent of the cardiac hypertrophy was evaluated by echocardiography and by pathological and molecular analyses of heart samples. Our results revealed that transgenic mice that overexpress miR-150 in the heart were resistant to cardiac hypertrophy and fibrosis through down-regulation of serum response factor (SRF). Conversely, the loss of function of miR-150 by genetic knockdown or antagomiR approaches produced the opposite effects. These studies suggest that miR-150 plays an important role in the regulation of cardiac hypertrophy and SRF is involved in miR-150 mediated anti-hypertrophic effect. Thus, miR-150 may be a new therapeutic target for cardiac hypertrophy. J. Cell. Biochem. 116: 2166-2176, 2015. (c) 2015 Wiley Periodicals, Inc.