MicroRNA-26 Was Decreased in Rat Cardiac Hypertrophy Model and May Be a Promising Therapeutic Target
MicroRNA-26 Was Decreased in Rat Cardiac Hypertrophy Model and May Be a Promising Therapeutic Target
复制标题
DOI：
10.1097/fjc.0b013e31829b82e6
复制
发表时间：
2013-09-01
影响因子：
3
通讯作者：
Liu, Shi-ming
中科院分区：
文献类型：
--
作者：
Zhang, Zhen-hui;Li, Jiao;Liu, Shi-ming
发现microRNA（miR）-26在心脏疾病中下调。在这项研究中，miR-26在体内和体外心肌肥大中的关键作用进行了研究。16只雄性Wistar大鼠随机分为对照组和腹主动脉缩窄术组。从新生Sprague-Dawley大鼠中分离心肌细胞。我们的研究表明miR-26 a/B在TAAC大鼠模型和心肌细胞中均下调。荧光素酶分析的结果还表明，糖原合成酶激酶3（GSK 3）可能是miR-26的直接靶点。miR-26的过表达减弱了GSK 3的表达并抑制了心肌肥厚。miR-26的下调逆转了这些作用。此外，GSK 3基因的沉默表型模仿了miR-26的抗肥大作用，而该蛋白的过表达减弱了miR-26的作用。综上所述，这些数据表明，miR-26调节大鼠心脏的病理结构变化，这可能与抑制GSK 3信号通路有关，并暗示miR-26在诊断和治疗心脏肥大中的潜在应用。
MicroRNA (miR)-26 was found to be downregulated in cardiac diseases. In this study, the critical role of miR-26 in myocardial hypertrophy in both in vivo and in vitro was investigated. Sixteen male Wistar rats that underwent sham or transverse abdominal aortic constriction (TAAC) surgery were divided into control or TAAC group. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats. Our study demonstrated that miR-26a/b was downregulated in both TAAC rat model and cardiomyocytes. The results of luciferase assays also suggested that glycogen synthase kinase 3 (GSK3) may be a direct target of miR-26. The overexpression of miR-26 attenuated GSK3 expression and inhibited myocardial hypertrophy. The downregulation of miR-26 reversed these effects. Furthermore, silence of GSK3 gene phenocopied the anti-hypertrophy effects of miR-26, whereas overexpression of this protein attenuated the effects of miR-26. Taken together, these data suggest that miR-26 regulates pathological structural changes in the rat heart, which may be associated with suppression of the GSK3 signaling pathway, and implicate the potential application of miR-26 in diagnosis and therapy of cardiac hypertrophy.