Effect and Mechanism of LRP6 on Cardiac Myocyte Ferroptosis in Myocardial Infarction.
Effect and Mechanism of LRP6 on Cardiac Myocyte Ferroptosis in Myocardial Infarction.
复制标题
LRP6对心肌梗死心肌细胞铁死亡的影响及机制
DOI：
10.1155/2021/8963987
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发表时间：
2021
影响因子：
--
通讯作者：
Kang S
中科院分区：
文献类型：
--
作者：
Li RL;Fan CH;Gong SY;Kang S
本研究旨在探讨LRP6在心肌梗死（MI）心肌细胞中调控铁凋亡的生物学功能和分子机制。我们建立了MI的体内和体外铁下垂模型，并通过生物信息学分析构建了circRNA-miRNA-LRP6的调控网络；然后，我们在RIP实验和双荧光素酶报告基因实验中重点探索LRP6及其上游基因circRNA1615和miR-152-3p的调控关系。我们还检测了LRP6介导的心肌细胞自噬相关的铁凋亡，发现心肌细胞存在铁凋亡，铁凋亡抑制剂铁抑素-1 （fer1）可以改善心肌细胞的病理过程，LRP6参与心肌细胞铁凋亡过程，LRP6的缺失通过自噬调节心肌细胞铁凋亡。上游基因circRNA1615的筛选和鉴定以LRP6为靶点。circRNA1615抑制心肌细胞铁凋亡，circRNA1615可以通过海绵吸附miR-152-3p调节LRP6的表达，阻止LRP6介导的心肌细胞自噬相关铁凋亡，最终控制心肌梗死的病理过程。circRNA1615通过miRNA152-3p/LRP6分子轴调控心肌细胞自噬抑制铁凋亡。
This study was aimed at exploring the biological function and molecular mechanism of ferroptosis of LRP6 modulation in cardiomyocytes of myocardial infarction (MI). We established the ferroptosis model of MI in vivo and in vitro and constructed the modulation network of circRNA-miRNA-LRP6 by bioinformatics analysis; then, we focused on exploring the regulatory relationship of LRP6 and its upstream genes circRNA1615 and miR-152-3p in the RIP experiments and the double luciferase reporter gene assay. Also, we tested the LRP6-mediated autophagy-related ferroptosis in MI. Ferroptosis was found in cardiomyocytes of MI, and ferroptosis inhibitor Ferrostatin-1 (Fer-1) could improve the pathological process of MI. LRP6 was involved in the process of ferroptosis in cardiomyocytes, and LRP6 deletion regulated ferroptosis in cardiomyocytes through autophagy. Screening and identification of the upstream gene circRNA1615 would target LRP6. circRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of MI. circRNA1615 inhibits ferroptosis via modulation of autophagy by the miRNA152-3p/LRP6 molecular axis in cardiomyocytes of myocardial infarction.
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