LRP6介导的连接蛋白43在心肌梗死中的磷酸化作用
LRP6-mediated phosphorylation of connexin43 in myocardial infarction.
作者信息
Zhang Xu-Min, Liu Ya-Ling, Cai Ying, Hao Ying, Kang Sheng
机构信息
Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road 150, Shanghai 200120, China.
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Pujian Road 160, Shanghai 200127, China.
出版信息
iScience. 2023 Feb 8;26(3):106160. doi: 10.1016/j.isci.2023.106160. eCollection 2023 Mar 17.
Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gα) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gα which played a role in VT of AMI.
室性心动过速（VT）和心室颤动是急性心肌梗死（AMI）患者早期死亡的主要原因。伴有连接蛋白43（Cx43）减少的条件性心脏特异性低密度脂蛋白受体相关蛋白6（LRP6）基因敲除小鼠会引发致命性室性心律失常。因此，有必要探究LRP6及其上游基因circRNA1615是否介导了AMI患者VT中Cx43的磷酸化。在此，我们发现circRNA1615通过海绵吸附miR-152-3p来调节LRP6 mRNA的表达。重要的是，LRP6干扰片段加重了Cx43的缺氧损伤，而LRP6的过表达则改善了Cx43的磷酸化。随后，干扰LRP6下游的G蛋白α亚基（Gα）进一步抑制了Cx43的磷酸化，并增加了VT的发生。我们的结果表明，LRP6上游基因circRNA1615控制了AMI中的损伤效应和VT，并且LRP6通过Gα介导Cx43的磷酸化，而Gα在AMI的VT中发挥作用。
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