Deletion of TECRL promotes skeletal muscle repair by up-regulating EGR2

Proc Natl Acad Sci U S A. 2024 May 21;121(21):e2317495121. doi: 10.1073/pnas.2317495121. Epub 2024 May 16.

Abstract

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further show that TECRL deletion led to the upregulation of the histone acetyltransferase general control nonderepressible 5, which enhances the transcription of EGR2 through acetylation. Importantly, we showed that AAV9-mediated TECRL silencing improved muscle repair in mice. These findings shed light on myogenic regeneration and muscle repair.

Keywords: ischemia; muscle regeneration; satellite cell.

MeSH terms

  • Animals
  • Cell Differentiation
  • Early Growth Response Protein 2* / genetics
  • Early Growth Response Protein 2* / metabolism
  • MAP Kinase Signaling System
  • Mice
  • Mice, Knockout
  • Muscle Development* / genetics
  • Muscle, Skeletal* / metabolism
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Regeneration* / genetics
  • Satellite Cells, Skeletal Muscle / metabolism
  • Up-Regulation

Substances

  • Egr2 protein, mouse
  • Pax7 protein, mouse