Association of YY1 with STING activation and the inflammatory response during early muscle injury repair

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2025-12-01 Epub Date: 2025-11-21 DOI:10.1016/j.molimm.2025.11.011

Xili Yan , Zhongxing Hou , Wenxin Li , Shuang Miao , Zejia Zhang , Jie Luo , Yinan Tao , Qiang Li , Jian Zhao , Zhiliang Xu

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引用次数: 0

Abstract

Background

Skeletal muscle injury is a common sports injury. Although the cGAS-STING signaling pathway is implicated in myoblast differentiation and muscle regeneration, its precise mechanisms remain unclear. Yin Yang 1 (YY1), a multifunctional transcriptional and chromatin regulator involved in various pathologies, also requires investigation for its specific role in regeneration.

Objectives

This study aimed to investigate the association between YY1 and cGAS-STING pathway activation during early muscle regeneration, and explore its potential role in the inflammatory phase of myoblast differentiation.

Methods

A skeletal muscle injury model was established in C57BL/6 mice using 1.2 % barium chloride. H&E staining evaluated muscle regeneration. Immunohistochemistry (IHC) quantified MyoG, YY1, H2Bub, and RNF20 expression. Immunofluorescence (IF) determined STING and YY1 expression. Western blotting measured cGAS, STING, YY1, caspase-3, IRF3, P-IRF3,P-TBK1, H2Bub and RNF20 protein levels. qPCR analyzed mRNA of inflammatory factors (IL-6, IL-17, IL-1β, TNF-α), myogenic regulators (MyoD, MyoG, Myf5), and signaling molecules (cGAS, STING, YY1, IRF3, caspase-3). Co-immunoprecipitation (Co-IP) assessed STING-YY1 interaction.

Results

Post-injury histology revealed significant pathology and inflammation. qPCR indicated upregulated mRNA levels of inflammatory factors and myogenic/signaling molecules at day 3, with partial recovery by day 7. Consistently, IHC (YY1, H2Bub, RNF20), IF (STING, YY1), and WB (cGAS, STING, YY1, caspase-3, IRF3, P-IRF3,P-TBK1, H2Bub and RNF20) all demonstrated elevated expression at day 3, declining by day 7. Co-IP confirmed a direct STING-YY1 interaction.

Conclusion

Our findings reveal a significant association between YY1 and cGAS-STING signaling activation, suggesting that this interplay contributes to the modulation of the inflammatory response during the early phase of skeletal muscle repair.

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YY1与早期肌肉损伤修复过程中STING激活和炎症反应的关系

骨骼肌损伤是一种常见的运动损伤。尽管cGAS-STING信号通路与成肌细胞分化和肌肉再生有关，但其确切机制尚不清楚。阴阳1 （YY1）是一种涉及多种病理的多功能转录和染色质调节因子，其在再生中的具体作用也需要研究。目的研究早期肌肉再生过程中YY1与cGAS-STING通路激活的关系，并探讨其在成肌细胞分化炎症期的潜在作用。方法采用1.2 %氯化钡建立C57BL/6小鼠骨骼肌损伤模型。H&；E染色评估肌肉再生。免疫组织化学（IHC）量化MyoG、YY1、H2Bub和RNF20的表达。免疫荧光（IF）检测STING和YY1的表达。Western blotting检测cGAS、STING、YY1、caspase-3、IRF3、P-IRF3、P-TBK1、H2Bub和RNF20蛋白水平。qPCR分析炎症因子（IL-6、IL-17、IL-1β、TNF-α）、肌生成调节因子（MyoD、MyoG、Myf5）和信号分子（cGAS、STING、YY1、IRF3、caspase-3）的mRNA表达。共免疫沉淀（Co-IP）评估STING-YY1相互作用。结果损伤后组织学显示明显的病理和炎症反应。qPCR显示，第3天炎症因子和肌源性/信号分子mRNA水平上调，第7天部分恢复。同样，IHC (YY1, H2Bub, RNF20), IF （STING, YY1）和WB （cGAS， STING, YY1, caspase-3, IRF3, P-IRF3,P-TBK1， H2Bub和RNF20）在第3天均表现出表达升高，到第7天下降。Co-IP确认了一个直接的STING-YY1交互。我们的研究结果揭示了YY1和cGAS-STING信号激活之间的显著关联，表明这种相互作用有助于在骨骼肌修复的早期阶段调节炎症反应。

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.