Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China.
Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China.
Life Sci. 2020 Aug 15;255:117817. doi: 10.1016/j.lfs.2020.117817. Epub 2020 May 21.
Glucocorticoids can promote cardiomyocyte maturation. However, the mechanism underlying glucocorticoid-mediated cardiomyocyte maturation is still unclear. Mitophagy plays a key role in cardiomyocyte maturation. Based on current knowledge, our study evaluated the effects of the glucocorticoid dexamethasone (100 nM) on the maturation of mouse embryonic stem cell-derived cardiomyocytes and the role of mitophagy in this maturation. The results showed that dexamethasone can promote embryonic stem cell-derived cardiomyocyte maturation, inhibit cardiomyocyte proliferation, and promote myocardial fiber arrangement. However, dexamethasone did not affect mitochondrial morphology in cardiomyocytes. Glucocorticoid receptor inhibitors (RU486, 1 nM) can inhibit dexamethasone-mediated cardiomyocyte maturation. Additionally, dexamethasone can promote mitophagy in embryonic stem cell-derived cardiomyocytes and induce LC3 and lysosomal aggregation in mitochondria. The inhibition of mitophagy can inhibit the cardiomyocyte maturation effect of dexamethasone. Furthermore, our research found that dexamethasone may mediate the occurrence of mitophagy in cardiomyocytes through Parkin. The siRNA-mediated inhibition of Parkin expression can inhibit mitochondrial autophagy caused by dexamethasone, thus inhibiting cardiomyocyte maturation. Overall, our study found that dexamethasone can promote embryonic stem cell-derived cardiomyocyte maturation through Parkin-mediated mitophagy.
糖皮质激素可促进心肌细胞成熟。然而，糖皮质激素介导的心肌细胞成熟的机制尚不清楚。线粒体自噬在心肌细胞成熟中起着关键作用。基于现有知识，我们的研究评估了糖皮质激素地塞米松（100 nM）对小鼠胚胎干细胞衍生的心肌细胞成熟的影响，以及线粒体自噬在这种成熟中的作用。结果表明，地塞米松可促进胚胎干细胞衍生的心肌细胞成熟，抑制心肌细胞增殖，促进心肌纤维排列。然而，地塞米松对心肌细胞中线粒体形态没有影响。糖皮质激素受体抑制剂（RU486，1 nM）可抑制地塞米松介导的心肌细胞成熟。此外，地塞米松可促进胚胎干细胞衍生的心肌细胞中的线粒体自噬，并诱导 LC3 和溶酶体在线粒体中的聚集。线粒体自噬的抑制可抑制地塞米松对心肌细胞成熟的作用。此外，我们的研究发现，地塞米松可能通过 Parkin 介导心肌细胞中线粒体自噬的发生。Parkin 表达的 siRNA 介导抑制可抑制地塞米松引起的线粒体自噬，从而抑制心肌细胞成熟。总体而言，我们的研究发现，地塞米松可通过 Parkin 介导的线粒体自噬促进胚胎干细胞衍生的心肌细胞成熟。
