Exercise Attenuates Doxorubicin-Induced Myocardial Injury by Inhibiting TSHR and Regulating Macrophage Polarization Through miR-30d-5p/GALNT7.

IF 3.5 3区 医学 Q2 IMMUNOLOGY Journal of Immunology Research Pub Date : 2024-10-26 eCollection Date: 2024-01-01 DOI:10.1155/2024/5562293
Haiyan Wu, Ruoyu Zhou, Hanxin Kong, Jieqiong Yang, Suijuan Liu, Xiaolin Wei, Kunzhi Li, Yunmei Zhang
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Abstract

Objective: Doxorubicin (DOX) is an extensively used chemotherapeutic agent that induces cardiotoxicity. Studies have reported that exercise (EXE) can alleviate DOX-induced cardiotoxicity. Therefore, this study aimed to explore the mechanism by which EXE attenuates DOX-induced myocardial injury. Methods: In this study, cell and animal models of DOX-induced myocardial injury were constructed. The animal model was subjected to EXE intervention. Results: In this study, in vitro experiments revealed that miR-30d-5p negatively regulated polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7) and that GALNT7 negatively regulated the expression of thyroid stimulating hormone receptor (TSHR). miR-30d-5p downregulated the expression of GALNT7, promoted the expression of TSHR, and promoted macrophage M1 polarization, thus aggravating cardiomyocyte injury. In vivo experiments revealed that EXE intervention significantly downregulated miR-30d-5p and TSHR expression, upregulated GALNT7, reduced inflammation, and promoted M2 macrophage polarization, thereby alleviating DOX-induced myocardial injury. In addition, overexpression of miR-30d-5p or knockdown of GALNT7 weakened the intervention effect of EXE, whereas overexpression of GALNT7 or knockdown of TSHR promoted the effect of EXE. Conclusion: EXE can modulate the miR-30d-5p/GALNT7 axis to inhibit the expression of TSHR, thereby regulating the polarization of macrophages to the M2 phenotype and ultimately alleviating DOX-induced myocardial injury, which provides new targets and strategies for the clinical treatment of myocardial injury.

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运动通过抑制 TSHR 并通过 miR-30d-5p/GALNT7 调节巨噬细胞极化来减轻多柔比星诱发的心肌损伤
目的:多柔比星(DOX)是一种广泛使用的化疗药物,可诱发心脏毒性。有研究报告称,运动(EXE)可减轻 DOX 诱导的心脏毒性。因此,本研究旨在探讨 EXE 减轻 DOX 诱导的心肌损伤的机制。研究方法本研究构建了 DOX 诱导的心肌损伤的细胞和动物模型。对动物模型进行EXE干预。结果本研究的体外实验发现,miR-30d-5p 负向调节多肽 N-乙酰半乳糖氨基转移酶 7(GALNT7),GALNT7 负向调节促甲状腺激素受体(TSHR)的表达,miR-30d-5p 下调 GALNT7 的表达,促进 TSHR 的表达,促进巨噬细胞 M1 极化,从而加重心肌细胞损伤。体内实验显示,EXE干预能显著下调miR-30d-5p和TSHR的表达,上调GALNT7,减轻炎症反应,促进M2巨噬细胞极化,从而减轻DOX诱导的心肌损伤。此外,过表达 miR-30d-5p 或敲除 GALNT7 会削弱 EXE 的干预效果,而过表达 GALNT7 或敲除 TSHR 则会促进 EXE 的效果。结论EXE能调节miR-30d-5p/GALNT7轴抑制TSHR的表达,从而调节巨噬细胞向M2表型极化,最终缓解DOX诱导的心肌损伤,为临床治疗心肌损伤提供了新的靶点和策略。
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来源期刊
CiteScore
6.90
自引率
2.40%
发文量
423
审稿时长
15 weeks
期刊介绍: Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology, molecular immunology, clinical immunology, cancer immunology, transplantation immunology, immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy.
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