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

作者全名："Kang, Xia; Qian, Jin; Shi, You-xing; Bian, Xu-ting; Zhang, Li-dan; Li, Gao-ming; Wang, Li-ting; Zhao, Jing; Dong, Zhen-yu; Yang, Meng-meng; Chen, Yu-Jia-Nan; Tang, Kang-lai; Miao, Hong-ming"

作者地址："[Kang, Xia; Qian, Jin; Miao, Hong-ming] Army Med Univ, Coll High Altitude Mil Med, Dept Pathophysiol, Chongqing 400038, Peoples R China; [Shi, You-xing; Bian, Xu-ting; Dong, Zhen-yu; Chen, Yu-Jia-Nan; Tang, Kang-lai] Army Med Univ, Affiliated Hosp 1, Dept Sports Med Ctr, State Key Lab Trauma Burn & Combined Injury, Chongqing 400038, Peoples R China; [Kang, Xia] Gen Hosp Western Theater Command, Pancreat Injury & Repair Key Lab Sichuan Prov, Chengdu 610000, Sichuan, Peoples R China; [Miao, Hong-ming] Jinfeng Lab, Chongqing 401329, Peoples R China; [Wang, Li-ting; Zhao, Jing] Army Med Univ, Biomed Anal Ctr, Chongqing 400038, Peoples R China; [Zhang, Li-dan; Yang, Meng-meng] Chongqing Med Univ, Ctr Med Epigenet, Sch Basic Med Sci, Chongqing 400038, Peoples R China; [Li, Gao-ming] Army Med Univ, Dept Hlth Stat, Chongqing 400038, Peoples R China"

通信作者："Kang, X; Miao, HM (通讯作者)，Army Med Univ, Coll High Altitude Mil Med, Dept Pathophysiol, Chongqing 400038, Peoples R China.; Tang, KL (通讯作者)，Army Med Univ, Affiliated Hosp 1, Dept Sports Med Ctr, State Key Lab Trauma Burn & Combined Injury, Chongqing 400038, Peoples R China.; Kang, X (通讯作者)，Gen Hosp Western Theater Command, Pancreat Injury & Repair Key Lab Sichuan Prov, Chengdu 610000, Sichuan, Peoples R China.; Miao, HM (通讯作者)，Jinfeng Lab, Chongqing 401329, Peoples R China."

来源：CELL STEM CELL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001181533300001

JCR分区：Q1

影响因子：23.9

年份：2024

卷号：31

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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/FILIP1Ldependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury."

基金机构："National Natural Science Foundation of China [82173134, 81872028, 82130071]; Jinfeng Laboratory; Science and Technology Department of Sichuan Province [2023ZYD0061]; China Postdoctoral Science Foundation [2020M673648]; Natural Science Foundation of Chongqing [cstc2020jcyj- msxmX0440]; Chongqing Postdoctoral Science Special Foundation"

基金资助正文："The authors would like to thank all the members of our laboratory for their work. This research was supported by the National Natural Science Foundation of China (82173134, 81872028, 82130071), the funding of the Jinfeng Laboratory, the funding of the Science and Technology Department of Sichuan Province (2023ZYD0061), the China Postdoctoral Science Foundation (2020M673648), the Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0440), and the Chongqing Postdoctoral Science Special Foundation."