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仿生电刺激通过 TGF-β1 在体外诱导大鼠骨髓间充质干细胞向心肌细胞样细胞分化。

Biomimetic electrical stimulation induces rat bone marrow mesenchymal stem cells to differentiate into cardiomyocyte-like cells via TGF-beta 1 in vitro.

机构信息

Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China; Laboratory Animal Center of Sichuan University, Chengdu 610041, China.

Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.

出版信息

Prog Biophys Mol Biol. 2019 Nov;148:47-53. doi: 10.1016/j.pbiomolbio.2017.09.023. Epub 2017 Sep 29.

Abstract

Electrical conductance is one of the factors of the microenvironment of cardiomyocytes, and electrical stimulation (ES) has been shown to modulate the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) toward a cardiomyogenic fate. Transforming growth factor-beta 1 (TGF-β1) stimulates the cardiomyogenic marker expression in BMSCs. Herein, we promoted the differentiation of BMSCs into cardiomyocyte-like cells using ES to confirm if TGF-β1 mediates this event in vitro. ES increased protein levels of TGF-β1 in BMSCs, and this effect was better than that observed with 5-azacytidine (5-Aza). The effect of ES on promoting cardiomyogenic marker expression in BMSCs was enhanced by TGF-β1. Furthermore, the protein expression levels of Connexin43 (Cx43) and Alpha-actinin 2 (ACTN2) induced by ES in BMSCs were significantly decreased by pirfenidone. These results show that ES promotes cardiomyocyte-like cells differentiation in rat BMSCs and is possibly mediated by TGF-β1 in vitro.

摘要

电导率是心肌细胞微环境的因素之一,电刺激 (ES) 已被证明可调节骨髓间充质干细胞 (BMSCs) 向心肌生成状态的分化。转化生长因子-β1 (TGF-β1) 刺激 BMSCs 中的心肌标志物表达。在此,我们使用 ES 促进 BMSCs 分化为心肌样细胞,以确认 TGF-β1 是否在体外介导了这一事件。ES 增加了 BMSCs 中 TGF-β1 的蛋白水平,其效果优于 5-氮杂胞苷 (5-Aza)。ES 对促进 BMSCs 中心肌标志物表达的作用可被 TGF-β1 增强。此外,ES 在 BMSCs 中诱导的 Connexin43 (Cx43) 和 Alpha-actinin 2 (ACTN2) 的蛋白表达水平可被吡非尼酮显著降低。这些结果表明 ES 可促进大鼠 BMSCs 中心肌样细胞的分化,并且可能是通过 TGF-β1 体外介导的。

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