*Intensive Care Unit; and †Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; ‡Guangzhou Institute of Cardiovascular Disease, Guangzhou, China; §Department of Physiology, Guangzhou Medical University, Guangzhou, China; and ¶Experimental Medicine Research Center, Guangzhou Medical University, Guangzhou, China.
J Cardiovasc Pharmacol. 2013 Sep;62(3):312-9. doi: 10.1097/FJC.0b013e31829b82e6.
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 3β (GSK3β) may be a direct target of miR-26. The overexpression of miR-26 attenuated GSK3β expression and inhibited myocardial hypertrophy. The downregulation of miR-26 reversed these effects. Furthermore, silence of GSK3β 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 GSK3β signaling pathway, and implicate the potential application of miR-26 in diagnosis and therapy of cardiac hypertrophy.
miR-26 在心脏疾病中被发现下调。在这项研究中，研究人员研究了 miR-26 在体内和体外心肌肥厚中的关键作用。16 只雄性 Wistar 大鼠接受假手术或横主动脉缩窄（TAAC）手术，分为对照组或 TAAC 组。从新生 Sprague-Dawley 大鼠中分离心肌细胞。我们的研究表明，miR-26a/b 在 TAAC 大鼠模型和心肌细胞中均下调。荧光素酶检测结果还表明，糖原合酶激酶 3β（GSK3β）可能是 miR-26 的直接靶标。miR-26 的过表达减弱了 GSK3β 的表达并抑制了心肌肥厚。miR-26 的下调逆转了这些效应。此外，GSK3β 基因的沉默模拟了 miR-26 的抗肥厚作用，而该蛋白的过表达则减弱了 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性结构变化，可能与抑制 GSK3β 信号通路有关，并暗示 miR-26 在心脏肥厚的诊断和治疗中有潜在的应用价值。
