IKZF1通过抑制MyoG转录负调控骨骼肌再生
IKZF1 negatively regulates skeletal muscle regeneration by repressing MyoG transcription
韩兴宇 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：探究IKZF1（Ikaros family zinc finger 1, IKZF1）在骨骼肌再生及卫星细胞功能调控中的作用与机制。方法：利用野生型小鼠缺血再灌注（Ischemia reperfusion, IR）损伤模型和卫星细胞体外分化模型检测IKZF1的表达变化；通过过表达Ikzf1或降解IKZF1蛋白双向探究其对卫星细胞增殖及肌源性分化的影响；采用染色质免疫沉淀（Chromatin immunoprecipitation assay, ChIP）和双荧光素酶报告基因实验分析IKZF1在卫星细胞中对肌源性相关因子的转录调控作用。结果：IKZF1在IR损伤后再生及卫星细胞分化早期均被短暂诱导后迅速下调；过表达Ikzf1抑制了卫星细胞的增殖活性并损害了其分化融合能力；来度那胺诱导的IKZF1降解增强了卫星细胞的增殖与分化能力；IKZF1可以直接结合MyoG（Myogenin, MyoG）启动子抑制其转录活性，从而抑制卫星细胞的终末分化。结论：IKZF1是骨骼肌再生的负向调控因子，通过介导MyoG的转录抑制损害了卫星细胞功能，进而阻碍了骨骼肌的再生进程。本研究在卫星细胞中揭示了IKZF1-MyoG转录抑制轴，为肌肉修复提供了新的机制见解和潜在治疗靶点。
Abstract
Objective: To investigate the role and mechanism of IKZF1 in skeletal muscle regeneration and the regulation of satellite cell function. Methods: The expression changes of IKZF1 were detected using a wild type mouse model of ischemia reperfusion (IR) injury and an in vitro satellite cell differentiation model. Functional impacts of IKZF1 on satellite cell proliferation and myogenic differentiation were investigated bidirectionally by overexpressing Ikzf1 or degrading the IKZF1 protein. ChIP and luciferase assays were performed to analyze the transcriptional regulation of myogenic related factors by IKZF1 in satellite cells. Results: The expression of IKZF1 was transiently induced and subsequently downregulated during both skeletal muscle regeneration after IR injury and early satellite cell differentiation. Overexpression of Ikzf1 suppressed the proliferative activity of satellite cells and impaired their differentiation and fusion capacity. Lenalidomide induced degradation of IKZF1 enhanced satellite cell proliferation and differentiation. Furthermore, IKZF1 directly bound to the MyoG (Myogenin) promoter and suppressed its transcriptional activity, thereby inhibiting terminal differentiation of satellite cells. Conclusions: IKZF1 is a negative regulator of skeletal muscle regeneration. It impairs satellite cell function by mediating transcriptional repression of MyoG, thereby hindering the process of skeletal muscle regeneration. This study reveals an IKZF1 MyoG transcriptional repressive axis in satellite cells, providing new mechanistic insights and a potential therapeutic target for muscle repair.关键词
细胞生物学/IKZF1/骨骼肌再生/缺血再灌注损伤/卫星细胞/MyoGKey words
Cell Biology/IKZF1/Skeletal muscle regeneration/Ischemia reperfusion injury/Satellite cells/MyoG引用本文复制引用
韩兴宇,宋耀华.IKZF1通过抑制MyoG转录负调控骨骼肌再生[EB/OL].(2026-07-03)[2026-07-05].http://www.paper.edu.cn/releasepaper/content/202607-8.学科分类
细胞生物学/生物科学研究方法、生物科学研究技术/分子生物学
