Department of Emergency Medicine, The Forth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Mol Cell Biochem. 2013 Jul;379(1-2):1-6. doi: 10.1007/s11010-012-1552-z. Epub 2013 May 10.
miRNAs play an important role in the pathogenesis of cardiac hypertrophy and dysfunction. However, little is known about how miR-30a regulates cardiomyocyte hypertrophy. In the study, Male C57BL/6 mice were subjected to thoracic aortic constriction, and hearts were harvested at 3 weeks. We assayed miR-30a expression level by real-time PCR and defined the molecular mechanisms of miR-30a-mediated cardiomyocyte hypertrophy. We found that myocardial expression of miR-30a was decreased in mouse models of hypertrophy and in H9c2 cells treated with phenylephrine. MiR-30a inhibition markedly increased mRNA expression of cardiac hypertrophy markers such as atrial natriuretic factor and brain natriuretic peptide in H9c2, and cell size was increased after miR-30a inhibitor treatment. Downregulated miR-30a activated autophagy by inhibiting beclin-1 expression in H9c2 cell. More important, autophagy inhibition suppressed miR-30a inhibitor-induced cardiomyocyte hypertrophy. Together, our data demonstrated that downregulated miR-30a aggravates pressure overload-induced cardiomyocyte hypertrophy by activating autophagy, thus offering a new target for the therapy of cardiomyocyte hypertrophy.
miRNAs 在心肌肥厚和功能障碍的发病机制中发挥重要作用。然而，miR-30a 如何调节心肌细胞肥大的机制尚不清楚。在这项研究中，雄性 C57BL/6 小鼠接受胸主动脉缩窄术，并在 3 周时采集心脏。我们通过实时 PCR 检测 miR-30a 的表达水平，并确定了 miR-30a 介导的心肌细胞肥大的分子机制。我们发现，在肥厚模型和苯肾上腺素处理的 H9c2 细胞中，心肌 miR-30a 的表达降低。miR-30a 抑制可显著增加 H9c2 中心脏肥大标志物如心房利钠肽和脑利钠肽的 mRNA 表达，并且在 miR-30a 抑制剂处理后细胞大小增加。下调的 miR-30a 通过抑制 H9c2 细胞中的 beclin-1 表达来激活自噬。更重要的是，自噬抑制抑制了 miR-30a 抑制剂诱导的心肌细胞肥大。总之，我们的数据表明，下调的 miR-30a 通过激活自噬加重压力超负荷诱导的心肌细胞肥大，为心肌细胞肥大的治疗提供了新的靶点。
