FOSL1在骨骼肌再生修复中的作用
The Role of FOSL1 in Skeletal Muscle Regeneration and Repair
马子昕 1宋耀华1
作者信息
- 1. 苏州大学唐仲英血液学研究中心，苏州，215123
- 折叠
摘要
目的：探讨FOS样抗原1（FOS-like antigen 1, FOSL1）在卫星细胞介导的骨骼肌再生中的作用及其分子机制。方法：采用流式细胞分选技术分离小鼠肌卫星细胞，结合免疫荧光染色明确FOSL1表达定位；通过小鼠后肢缺血再灌注（Ischemia-Reperfusion, IR）损伤模型及体外诱导卫星细胞分化，检测FOSL1在骨骼肌再生中的表达特征；利用慢病毒介导的基因过表达技术，在C2C12成肌细胞及卫星细胞中稳定过表达Fosl1，观察其对肌源性细胞增殖与分化表型的影响；进一步通过染色质免疫沉淀及双荧光素酶报告基因实验，探究FOSL1通过转录调控Pax7和MyoD影响该过程的分子机制。结果：FOSL1定位于卫星细胞核，骨骼肌IR损伤后早期快速诱导表达，但随卫星细胞分化逐渐下调；Fosl1过表达促进C2C12成肌细胞及卫星细胞增殖同时抑制其分化；FOSL1结合Pax7启动子并激活其转录，结合MyoD启动子但抑制其转录。结论：FOSL1在骨骼肌损伤早期被快速诱导，通过差异性调控Pax7和MyoD转录，协调肌源性细胞增殖与分化平衡，是骨骼肌再生的关键调控因子。
Abstract
Objective: To investigate the role and molecular mechanism of FOS like antigen 1 (FOSL1) in satellite cell-mediated skeletal muscle regeneration. Methods: Mouse muscle satellite cells were isolated by flow cytometry, and the localization of FOSL1 expression was determined by immunofluorescence staining. The expression characteristics of FOSL1 during skeletal muscle regeneration were detected by a mouse hindlimb ischemia-reperfusion (IR) injury model and in vitro induction of satellite cell differentiation. Using lentivirus-mediated gene overexpression technology, Fosl1 was stably overexpressed in C2C12 myoblasts and satellite cells, and its effects on the proliferation and differentiation phenotype of myogenic cells were observed. The molecular mechanism of FOSL1 affecting this process by transcriptional regulation of Pax7 and MyoD was further explored through chromatin immunoprecipitation and dual-luciferase reporter assay. Results: FOSL1 is localized in the nuclei of satellite cells, rapidly induced in the early stage after skeletal muscle IR injury, but gradually downregulated with satellite cell differentiation. Fosl1 overexpression promotes the proliferation of C2C12 myoblasts and satellite cells while inhibiting their differentiation. FOSL1 binds to the Pax7 promoter and activates its transcription, and binds to the MyoD promoter while represses its transcription. Conclusion: FOSL1 is rapidly induced in the early stage of skeletal muscle injury and coordinates the balance of myogenic cell proliferation and differentiation by differentially regulating the transcription of Pax7 and MyoD, serving as a key regulatory factor in skeletal muscle regeneration.关键词
FOSL1/骨骼肌IR损伤/肌卫星细胞/肌肉再生Key words
FOSL1/skeletal muscle IR injury/muscle satellite cells/muscle regeneration引用本文复制引用
马子昕,宋耀华.FOSL1在骨骼肌再生修复中的作用[EB/OL].(2026-07-03)[2026-07-05].http://www.paper.edu.cn/releasepaper/content/202607-7.学科分类
分子生物学/生物科学研究方法、生物科学研究技术
