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脉冲电磁场联合脂肪源性干细胞通过调节 miR-20a-5p/E2F1/p73 信号保护缺血性心肌。

Pulsed Electromagnetic Fields Combined With Adipose-Derived Stem Cells Protect Ischemic Myocardium by Regulating miR-20a-5p/E2F1/p73 Signaling.

机构信息

Department of Rehabilitation Medicine and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, People's Republic of China.

出版信息

Stem Cells. 2023 Jul 14;41(7):724-737. doi: 10.1093/stmcls/sxad037.

Abstract

Myocardial infarction (MI) is a serious threat to human health. Although monotherapy with pulsed electromagnetic fields (PEMFs) or adipose-derived stem cells (ADSCs) has been reported to have positive effect on the treatment of MI, a satisfactory outcome has not yet been achieved. In recent years, combination therapy has attracted widespread interest. Herein, we explored the synergistic therapeutic effect of combination therapy with PEMFs and ADSCs on MI and found that the combination of PEMFs and ADSCs effectively reduced infarct size, inhibited cardiomyocyte apoptosis and protected the cardiac function in mice with MI. In addition, bioinformatics analysis and RT-qPCR showed that the combination therapy could affect apoptosis by regulating the expression of miR-20a-5p. A dual-luciferase reporter gene assay also confirmed that the miR-20a-5p could target E2F transcription factor 1 (E2F1) and inhibit cardiomyocyte apoptosis by regulating the E2F1/p73 signaling pathway. Therefore, our study systematically demonstrated the effectiveness of combination therapy on the inhibition of cardiomyocyte apoptosis by regulating the miR-20a-5p/E2F1/p73 signaling pathway in mice with MI. Thus, our study underscored the effectiveness of the combination of PEMFs and ADSCs and identified miR-20a-5p as a promising therapeutic target for the treatment of MI in the future.

摘要

心肌梗死(MI)是严重威胁人类健康的疾病。虽然脉冲电磁场(PEMFs)或脂肪来源的干细胞(ADSCs)的单独治疗已被报道对 MI 的治疗有积极作用,但尚未达到令人满意的效果。近年来,联合治疗引起了广泛关注。在此,我们探讨了 PEMFs 和 ADSCs 联合治疗对 MI 的协同治疗效果,发现 PEMFs 和 ADSCs 的联合有效减少了梗死面积,抑制了心肌细胞凋亡,保护了 MI 小鼠的心脏功能。此外,生物信息学分析和 RT-qPCR 表明,联合治疗可以通过调节 miR-20a-5p 的表达来影响细胞凋亡。双荧光素酶报告基因实验也证实了 miR-20a-5p 可以通过调节 E2F 转录因子 1(E2F1)/p73 信号通路来靶向 E2F1 并抑制心肌细胞凋亡。因此,我们的研究系统地证明了联合治疗通过调节 miR-20a-5p/E2F1/p73 信号通路抑制 MI 小鼠心肌细胞凋亡的有效性。因此,我们的研究强调了 PEMFs 和 ADSCs 联合治疗的有效性,并确定了 miR-20a-5p 作为未来 MI 治疗有前途的治疗靶点。

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