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Delta 样 1 同源物对小鼠模型肌肉萎缩的保护作用。

Protective Effect of Delta-Like 1 Homolog Against Muscular Atrophy in a Mouse Model.

机构信息

Department of Molecular, Cellular and Cancer Biology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Endocrinol Metab (Seoul). 2022 Aug;37(4):684-697. doi: 10.3803/EnM.2022.1446. Epub 2022 Aug 29.

DOI:10.3803/EnM.2022.1446
PMID:36065648
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9449104/
Abstract

BACKGRUOUND

Muscle atrophy is caused by an imbalance between muscle growth and wasting. Delta-like 1 homolog (DLK1), a protein that modulates adipogenesis and muscle development, is a crucial regulator of myogenic programming. Thus, we investigated the effect of exogenous DLK1 on muscular atrophy.

METHODS

We used muscular atrophy mouse model induced by dexamethasone (Dex). The mice were randomly divided into three groups: (1) control group, (2) Dex-induced muscle atrophy group, and (3) Dex-induced muscle atrophy group treated with DLK1. The effects of DLK1 were also investigated in an in vitro model using C2C12 myotubes.

RESULTS

Dex-induced muscular atrophy in mice was associated with increased expression of muscle atrophy markers and decreased expression of muscle differentiation markers, while DLK1 treatment attenuated these degenerative changes together with reduced expression of the muscle growth inhibitor, myostatin. In addition, electron microscopy revealed that DLK1 treatment improved mitochondrial dynamics in the Dex-induced atrophy model. In the in vitro model of muscle atrophy, normalized expression of muscle differentiation markers by DLK1 treatment was mitigated by myostatin knockdown, implying that DLK1 attenuates muscle atrophy through the myostatin pathway.

CONCLUSION

DLK1 treatment inhibited muscular atrophy by suppressing myostatin-driven signaling and improving mitochondrial biogenesis. Thus, DLK1 might be a promising candidate to treat sarcopenia, characterized by muscle atrophy and degeneration.

摘要

背景

肌肉萎缩是由肌肉生长和消耗失衡引起的。Delta-like 1 同源物（DLK1）是一种调节脂肪生成和肌肉发育的蛋白质，是肌生成编程的关键调节因子。因此，我们研究了外源性 DLK1 对肌肉萎缩的影响。

方法

我们使用地塞米松（Dex）诱导的肌肉萎缩小鼠模型。将小鼠随机分为三组：（1）对照组，（2）Dex 诱导的肌肉萎缩组，（3）Dex 诱导的肌肉萎缩组用 DLK1 处理。还在 C2C12 肌管的体外模型中研究了 DLK1 的作用。

结果

Dex 诱导的小鼠肌肉萎缩与肌肉萎缩标志物的表达增加和肌肉分化标志物的表达减少有关，而 DLK1 治疗减轻了这些退化变化，同时降低了肌肉生长抑制剂肌生成素的表达。此外，电子显微镜显示，DLK1 治疗改善了 Dex 诱导的萎缩模型中的线粒体动力学。在肌肉萎缩的体外模型中，DLK1 处理通过肌生成素敲低使肌肉分化标志物的表达正常化，这表明 DLK1 通过肌生成素途径减轻肌肉萎缩。

结论

DLK1 通过抑制肌生成素驱动的信号通路和改善线粒体生物发生来抑制肌肉萎缩。因此，DLK1 可能是治疗以肌肉萎缩和退化为特征的肌肉减少症的有前途的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e3/9449104/4adb18d97eed/enm-2022-1446f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e3/9449104/4adb18d97eed/enm-2022-1446f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e3/9449104/46429b92f4d4/enm-2022-1446f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e3/9449104/4adb18d97eed/enm-2022-1446f7.jpg

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