Department of Cardiovascular Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
Inflammation. 2021 Aug;44(4):1581-1591. doi: 10.1007/s10753-021-01443-w. Epub 2021 Mar 2.
Activation of CX43 signaling protects myocardial cells from myocardial ischemia/reperfusion (I/R) injury. However, the underlying mechanism remains unclear. MicroRNAs (miRNAs) are well known to play important roles in the progression of diverse diseases. Here, we first confirmed the expression profile of CX43 in rat heart tissues with I/R injury. Then, microRNAs (miRNAs) that target CX43 were predicted using miRDB, miRWalk, and TargetScan. The candidate miR-23a was selected, and its expression level in I/R samples was investigated. To determine the role of miR-23a, rat primary myocardial cells were transfected with miR-23a mimics after they were subjected to hypoxia-reoxygenation (H/R) injury. Transfection of miR-23a mimics stimulated mitophagy through the PINK1/Parkin pathway and downregulated the protein level of CX43. Treatment of miR-23a-transfected cells with NF-kB inhibitors completely abolished miR-23a-mediated mitophagy after H/R. Moreover, miR-23a transfection significantly suppressed CX43 expression and enhanced mitophagy in the model heart in vivo. Therefore, miR-23a plays a detrimental role in myocardial I/R injury by enhancing mitophagy and inhibiting CX43 mRNA.
CX43 信号的激活可保护心肌细胞免受心肌缺血/再灌注（I/R）损伤。然而，其潜在机制尚不清楚。微小 RNA（miRNA）在多种疾病的进展中起着重要作用。在这里，我们首先证实了 CX43 在大鼠心肌组织 I/R 损伤中的表达谱。然后，使用 miRDB、miRWalk 和 TargetScan 预测了靶向 CX43 的 microRNAs (miRNAs)。选择候选 miR-23a，并研究其在 I/R 样本中的表达水平。为了确定 miR-23a 的作用，在大鼠原代心肌细胞经历缺氧再复氧（H/R）损伤后，用 miR-23a 模拟物进行转染。miR-23a 模拟物的转染通过 PINK1/Parkin 途径刺激自噬，并下调 CX43 蛋白水平。用 NF-kB 抑制剂处理转染 miR-23a 的细胞后，完全消除了 H/R 后 miR-23a 介导的自噬。此外，miR-23a 转染显著抑制了体内模型心脏中的 CX43 表达并增强了自噬。因此，miR-23a 通过增强自噬和抑制 CX43 mRNA 在心肌 I/R 损伤中发挥有害作用。
