Bao Q, Chen L, Li J, Zhao M, Wu S, Wu W, Liu X
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
Cell Mol Biol (Noisy-le-grand). 2017 Apr 29;63(4):23-27. doi: 10.14715/cmb/2017.63.4.4.
Cardiac hypertrophy is a crucial predictor of heart failure and is regulated by microRNAs. MicroRNA-124 (miR-124) is regarded as a prognostic indicator for outcomes after cardiac arrest. However, whether miR-124 participates in cardiac hypertrophy remains unclear. Therefore, our study aimed to determine the role of miR-124 in angiotensin II(AngII)-induced myocardial hypertrophy and the possible mechanism. Primary cultured rat neonatal cardiomyocytes(NCMs) were transfected with miR-124 mimics or inhibitor, followed by AngII stimulation. Quantitative RT-PCR, western blot analysis and determination of cell surface area of NCMs were used to detect the hypertrophic phenotypes. We observed that miR-124 was elevated in AngII-induced hypertrophic cardiomyocytes. Cell surface area of NCMs and mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC), indicators of myocardial hypertrophy, were higher in NCMs transfected with miR-124 mimics in the presence of AngII. On the contrary, knockdown of miR-124 by its specific inhibitor could restore these courses. Furthermore, downregulation of miR-124 alleviated the increased protein level of endoplasmic reticulum (ER) stress markers 78-kDa glucose-regulated protein (Grp78) and calreticulin(CRT) in AngII-induced NCMs. In conclusion, our study shows that inhibition of miR-124 effectively suppresses AngII-induced myocardial hypertrophy, which is associated with attenuation of ER stress.
心肌肥厚是心力衰竭的关键预测指标，且受微小RNA调控。微小RNA-124（miR-124）被视为心脏骤停后预后结果的一个指标。然而，miR-124是否参与心肌肥厚仍不清楚。因此，我们的研究旨在确定miR-124在血管紧张素II（AngII）诱导的心肌肥厚中的作用及可能机制。将miR-124模拟物或抑制剂转染原代培养的大鼠新生心肌细胞（NCMs），随后进行AngII刺激。采用定量逆转录聚合酶链反应、蛋白质印迹分析及测定NCMs的细胞表面积来检测肥厚表型。我们观察到在AngII诱导的肥厚心肌细胞中miR-124升高。在AngII存在的情况下，转染miR-124模拟物的NCMs的细胞表面积以及心肌肥厚指标心房钠尿肽（ANP）、脑钠尿肽（BNP）和β-肌球蛋白重链（β-MHC）的mRNA表达更高。相反，用其特异性抑制剂敲低miR-124可使这些过程恢复正常。此外，下调miR-124可减轻AngII诱导的NCMs中内质网（ER）应激标志物78-kDa葡萄糖调节蛋白（Grp78）和钙网蛋白（CRT）升高的蛋白水平。总之，我们的研究表明抑制miR-124可有效抑制AngII诱导的心肌肥厚，这与ER应激的减轻有关。
