Department of Cardiovascular Medicine, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
Jinzhou Hospital of Traditional Chinese Medicine, No. 91, Shifu Road, Taihe District, Jinzhou, Liaoning, 121000, China.
BMC Cardiovasc Disord. 2024 Oct 10;24(1):547. doi: 10.1186/s12872-024-04197-z.
Myocardial infarction (MI) remains a significant global health concern, characterized by cardiomyocyte apoptosis and adverse ventricular remodeling. Nevertheless, the interplay between exosomal miR-21-5p and Yes-associated protein 1 (YAP1) in the context of MI remains unexplored.
Rat mesenchymal stem cells (MSCs) and H9c2 cardiomyocytes were cultured, characterized, and instrumental in our experiments. Exosomes were meticulously isolated, and their identity confirmed. The internalization of these exosomes by H9c2 cells was assessed, while RNA and protein expression were quantified using Quantitative Real-Time PCR and Western blot, respectively. MTT assay was implemented for cell viability, and apoptosis was evaluated via flow cytometric analysis. To elucidate gene interactions, we conducted microarray profiling of miRNA expression, dual luciferase reporter assays, and RNA Immunoprecipitation.
MSC-derived exosomes exhibited a remarkable capacity to attenuate hypoxia-induced inflammation and apoptosis in H9c2 cells. Notably, these exosomes significantly upregulated miR-21-5p levels within H9c2 cells, and the abrogation of miR-21-5p function abated their protective effects. Through computational analysis, we unveiled a miR-21-5p binding site in the 3'UTR of YAP1, which directly inhibited YAP1 expression. Importantly, the inhibition of YAP1 effectively reinstated the protective effects of exosomes in cells with impaired exosomal miR-21-5p.
This study underscores the pivotal role played by MSC-derived exosomes in safeguarding against MI, primarily by mediating the transfer of miR-21-5p, which targets YAP1 signaling pathways.
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心肌梗死（MI）仍然是一个重大的全球健康问题，其特征是心肌细胞凋亡和心室重构不良。然而，miR-21-5p 外泌体与 Yes 相关蛋白 1（YAP1）在 MI 背景下的相互作用仍未被探索。
培养大鼠间充质干细胞（MSCs）和 H9c2 心肌细胞，并对其进行特征鉴定，这些细胞在我们的实验中发挥了重要作用。精心分离外泌体，并确认其身份。评估这些外泌体被 H9c2 细胞内化的情况，同时使用定量实时 PCR 和 Western blot 分别定量 RNA 和蛋白质表达。通过 MTT 测定评估细胞活力，通过流式细胞术分析评估细胞凋亡。为了阐明基因相互作用，我们进行了 miRNA 表达的微阵列分析、双荧光素酶报告基因测定和 RNA 免疫沉淀。
MSC 来源的外泌体表现出显著减轻 H9c2 细胞缺氧诱导的炎症和凋亡的能力。值得注意的是，这些外泌体显著上调了 H9c2 细胞内 miR-21-5p 的水平，而 miR-21-5p 功能的阻断减弱了它们的保护作用。通过计算分析，我们发现了 YAP1 的 3'UTR 中有一个 miR-21-5p 的结合位点，它直接抑制了 YAP1 的表达。重要的是，YAP1 的抑制有效恢复了缺失外泌体 miR-21-5p 的细胞中外泌体的保护作用。
这项研究强调了 MSC 衍生的外泌体在保护心肌免受损伤中的关键作用，主要是通过介导 miR-21-5p 的转移，该 miR-21-5p 靶向 YAP1 信号通路。
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