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LRP6 对心肌梗死后心肌细胞铁死亡的作用及机制。

Effect and Mechanism of LRP6 on Cardiac Myocyte Ferroptosis in Myocardial Infarction.

机构信息

Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road 150, Shanghai 200120, China.

School of Medicine, Tongji University, Siping Road 1239, Shanghai 200092, China.

出版信息

Oxid Med Cell Longev. 2021 Oct 19;2021:8963987. doi: 10.1155/2021/8963987. eCollection 2021.

DOI:10.1155/2021/8963987
PMID:34712388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8548150/
Abstract

BACKGROUND

This study was aimed at exploring the biological function and molecular mechanism of ferroptosis of LRP6 modulation in cardiomyocytes of myocardial infarction (MI).

METHOD

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.

RESULTS

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.

CONCLUSIONS

circRNA1615 inhibits ferroptosis via modulation of autophagy by the miRNA152-3p/LRP6 molecular axis in cardiomyocytes of myocardial infarction.

摘要

背景

本研究旨在探讨 LRP6 调节在心肌梗死（MI）心肌细胞中铁死亡中的生物学功能和分子机制。

方法

我们通过生物信息学分析建立了体内和体外 MI 铁死亡模型，并构建了 circRNA-miRNA-LRP6 调控网络；然后，我们集中探讨了 RIP 实验和双荧光素酶报告基因检测中 LRP6 及其上游基因 circRNA1615 和 miR-152-3p 的调控关系。此外，我们还检测了 LRP6 介导的 MI 中铁死亡相关自噬。

结果

发现 MI 心肌细胞中存在铁死亡，铁死亡抑制剂 Ferrostatin-1（Fer-1）可改善 MI 的病理过程。LRP6 参与心肌细胞中铁死亡过程，LRP6 缺失通过自噬调节心肌细胞中铁死亡。上游基因 circRNA1615 的筛选和鉴定会靶向 LRP6。circRNA1615 抑制心肌细胞铁死亡，circRNA1615 通过 miR-152-3p 的海绵吸附作用调节 LRP6 的表达，防止 LRP6 介导的心肌细胞自噬相关铁死亡，从而控制 MI 的病理过程。

结论

circRNA1615 通过 miRNA152-3p/LRP6 分子轴调节自噬，抑制心肌细胞铁死亡，从而控制心肌梗死中的铁死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/562a736ebd65/OMCL2021-8963987.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/84f9c5e18163/OMCL2021-8963987.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/a5e44ed14ad5/OMCL2021-8963987.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/0211146a0840/OMCL2021-8963987.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/562a736ebd65/OMCL2021-8963987.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/84f9c5e18163/OMCL2021-8963987.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/6ff86bb5632b/OMCL2021-8963987.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/de1cb52c54cb/OMCL2021-8963987.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/0211146a0840/OMCL2021-8963987.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08f7/8548150/562a736ebd65/OMCL2021-8963987.007.jpg

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