Title : Molecular mechanisms of skeletal muscle regeneration after ischemia reperfusion injury
Abstract:
Skeletal muscle is a dynamic tissue endowed with exceptional plasticity and robust regenerative potential, which largely depends on satellite cells (SCs) residing between the muscle basement membrane and sarcolemma. The biogenesis, differentiation, and self-renewal of satellite cells are primarily governed by the transcription factor paired box protein 7 (Pax7). TECRL (Trans-2,3-Enoyl-CoA Reductase Like) is an endoplasmic reticulum-resident protein predominantly expressed in cardiac and skeletal muscle. Mutations causing TECRL deficiency have been linked to cardiac arrhythmias and sudden cardiac death. Nevertheless, the biological function of TECRL in skeletal muscle regeneration remains largely unknown. In this study, we observed elevated TECRL expression following skeletal muscle ischemia–reperfusion (IR) injury. TECRL was primarily localized in satellite cells, with distribution in both the nucleus and cytoplasm. During satellite cell differentiation, TECRL expression gradually increased and exhibited an inverse correlation with Pax7 expression. Specific deletion of TECRL in satellite cells accelerated skeletal muscle regeneration via an EGR2-dependent mechanism. At the molecular level, TECRL modulated EGR2 expression through the ERK1/2 signaling cascade, thereby negatively regulating Pax7 transcription and skeletal muscle repair. Furthermore, TECRL depletion upregulated GCN5 (general control nonderepressible 5), which promoted EGR2 transcription through histone acetylation. Acetylated EGR2 subsequently bound to the Pax7 promoter and augmented Pax7 expression. Collectively, these results uncover a novel regulatory axis of TECRL–GCN5–EGR2–Pax7 in myogenic differentiation and skeletal muscle regeneration, providing new insights into the molecular control of muscle repair.
