运动诱导的肌肉蛋白决定纤维脂肪生成祖细胞的命运,从而控制肌肉稳态

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING
Xia Kang, Jin Qian, You-xing Shi, Xu-ting Bian, Li-dan Zhang, Gao-ming Li, Li-ting Wang, Jing Zhao, Zhen-yu Dong, Meng-meng Yang, Yu-Jia-Nan Chen, Kang-lai Tang, Hong-ming Miao
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引用次数: 0

摘要

运动对纤维脂肪生成祖细胞(FAPs)的影响尚不清楚,直接的分子联系也尚不明确。在这项研究中,我们揭示了运动可降低 FAPs 的频率,并通过 Musclin 减缓损伤或废用肌肉中胶原蛋白的沉积和脂肪的形成。从机理上讲,Musclin 通过上调 FILIP1L 抑制 FAP 的增殖并促进其凋亡。染色质免疫共沉淀(ChIP)-qPCR证实FoxO3a是FILIP1L的转录因子。此外,Musclin/FILIP1L 通路通过下调 CD47 的表达促进巨噬细胞吞噬凋亡的 FAPs。FILIP1L 在 FAPs 中的基因消减会消除运动或 Musclin 对 FAPs 的影响,以及对减少纤维化和脂肪浸润的益处。总之,运动会在肌肉中形成肌动素的微环境,并以依赖 Musclin/FILIP1L 的方式防止 FAPs 的异常积累。施用外源性 Musclin 可产生治疗效果,是治疗肌肉萎缩或急性肌肉损伤的一种潜在方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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