What question did this study set out to answer?

This research aims to clarify how the cGAS/STING pathway influences skeletal muscle regeneration after injury.

April 16, 2026Cellular & Molecular Biology Letters0 citationsOpen Access

The role of the cGAS/STING pathway in skeletal muscle regeneration: modulation of inflammation, macrophage polarization, and oxidative stress

XLXiaoguang LiuGuangzhou Sport University HWHao WangNorth China University of Science and Technology MXMan XuSouthwest University

Key Points

This research aims to clarify how the cGAS/STING pathway influences skeletal muscle regeneration after injury.
Induced skeletal muscle injury via cardiotoxin injection in mice.
Utilized genetic knockout models for cGAS and STING.
Administered a STING agonist (DMXAA) to assess pathway effects.
Conducted histological analysis and flow cytometry to assess tissue and immune responses.
Performed RNA extraction and gene expression analysis for inflammatory markers.
Injury significantly increased STING expression in muscle tissue.
STING agonist treatment reduced muscle fiber size and increased inflammation.
Knockout of cGAS or STING improved muscle regeneration and enhanced anti-inflammatory macrophage accumulation.
High pro-inflammatory macrophage infiltration and oxidative stress were observed with STING activation.

Abstract

Skeletal muscle regeneration is essential for restoring muscle structure and function following injury. This process is influenced by various signaling pathways. Recent studies suggest that cGAS/STING signaling, which is known for its role in innate immunity, may also play a crucial role in tissue regeneration. This study investigated the regulatory role of the cGAS/STING pathway in skeletal muscle regeneration. Skeletal muscle injury was induced via intramuscular injection of cardiotoxin (CTX) into the tibialis anterior (TA) muscle of mice. Genetic knockout models of cGAS and STING, as well as treatment with a STING agonist (DMXAA), were used to explore the role of the pathway in muscle regeneration. Histological analysis, flow cytometry, RNA extraction, and gene expression analysis were performed to evaluate muscle tissue morphology, macrophage infiltration, and the expression of inflammatory and oxidative stress markers. STING expression was significantly increased following injury. Treatment with a STING agonist impaired muscle regeneration, characterized by reduced muscle fiber dimensions, elevated pro-inflammatory macrophage infiltration, and increased oxidative stress. In contrast, cGAS or STING knockout enhanced muscle regeneration and promoted the accumulation of anti-inflammatory macrophages. The cGAS/STING pathway plays a critical role in skeletal muscle regeneration by influencing inflammation, macrophage polarization, and oxidative stress.

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