PDF(Pubmed)
Abstract：
Cardiac hypertrophy, worldwide known as an adaptive functional compensatory state of myocardial stress, is mainly believed to proceed to severe heart diseases, even to sudden death. Emerging studies have explored the microRNA alteration during hypertrophy. However, the mechanisms of microRNAs involved in cardiac hypertrophy are still uncertain. We studied young rats to establish abdominal aorta coarctation (AAC) for 4 weeks. With the significant downregulated cardiac function and upregulated hypertrophic biomarkers, AAC-induced rats showed enlarged myocardiocytes and alterations in microRNAs, especially downregulated miR-31-5p. miR-31-5p targets the 3\'UTR of Nfatc2ip and inhibits myocardial hypertrophy in vitro and in vivo. Furthermore, we verified that Nfatc2ip is necessary and sufficient for cardiac hypertrophy in neonatal rat cardiomyocytes. Moreover, we found miR-31-5p inhibited the colocalization of Nfatc2ip and hypertrophic gene β-Mhc. Luciferase assay and ChiP-qPCR test demonstrated that Nfatc2ip binded to the core-promoter of β-Mhc and enhanced its transcriptional activity. Above all, our study found a new pathway, mir-31-5p/Nfatc2ip/β-Mhc, which is involved in cardiac hypertrophy, suggesting a potential target for intervention of cardiac hypertrophy.
摘要：
心脏肥大,世界范围内称为心肌应激的适应性功能代偿状态，主要被认为是严重的心脏病，甚至突然死亡。新兴的研究已经探索了肥大过程中microRNA的改变。然而,微小RNA参与心肌肥厚的机制尚不明确。我们研究了幼年大鼠建立腹主动脉缩窄（AAC）4周。随着显著下调的心功能和上调的肥大生物标志物，AAC诱导的大鼠显示心肌细胞增大和microRNAs的改变，尤其是下调的miR-31-5p。miR-31-5p靶向Nfatc2ip的3'UTR并在体外和体内抑制心肌肥大。此外，我们验证了Nfatc2ip对于新生大鼠心肌细胞的心肌肥大是必要且足够的。此外，我们发现miR-31-5p抑制Nfatc2ip和肥大基因β-Mhc的共定位。荧光素酶测定和ChiP-qPCR测试表明Nfatc2ip与β-Mhc的核心启动子结合并增强其转录活性。最重要的是,我们的研究发现了一条新的途径,mir-31-5p/Nfatc2ip/β-Mhc，这与心脏肥大有关，提示心脏肥大干预的潜在目标。
