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<p>The muscle stem cell niche is well-described as influencing myogenic cell fate decision; however, the intrinsic mechanisms driving muscle stem cell progression during myogenesis are not yet fully elucidated. Here, we demonstrate that bioactive lipid class switching, an auto-regulatory mechanism originally described during the inflammatory process, is conserved during myogenesis. During the transition from proliferation to differentiation, myogenic cells shift from pro-inflammatory to pro-resolution pathways, a process partially mediated by 15Δ-PGJ<sub>2</sub> that promotes the expression of the&#xa0;prostaglandin inactivation enzyme 15-hydroxyprostaglandin dehydrogenase. Using pharmacological inhibitors and knockout models&#xa0;of the pro-resolution enzyme&#xa0;15-lipoxygenase, we show that blocking the bioactive lipid class switching impairs myoblast differentiation in vitro and muscle regeneration in vivo. Administration of the pro-resolving mediator Protectin-D1 restores myogenesis, enhances muscle regeneration post-injury and improves muscle phenotype in a dystrophic mouse model. Overall, these findings provide a better comprehension of the mechanisms regulating myogenic progression, which opens new therapeutic avenues for muscle regeneration and dystrophies.</p>

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Bioactive lipid mediator class switching regulates myogenic cell progression and muscle regeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

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  • Paul Fabre,
  • Thomas Molina,
  • Jessica Larose,
  • Karine Greffard,
  • Gregory Généreux-Gamache,
  • Alyson Deprez,
  • Inès Mokhtari,
  • Ornella Pellerito,
  • Elise Duchesne,
  • Junio Dort,
  • Jean-François Bilodeau,
  • Nicolas A. Dumont

摘要

The muscle stem cell niche is well-described as influencing myogenic cell fate decision; however, the intrinsic mechanisms driving muscle stem cell progression during myogenesis are not yet fully elucidated. Here, we demonstrate that bioactive lipid class switching, an auto-regulatory mechanism originally described during the inflammatory process, is conserved during myogenesis. During the transition from proliferation to differentiation, myogenic cells shift from pro-inflammatory to pro-resolution pathways, a process partially mediated by 15Δ-PGJ2 that promotes the expression of the prostaglandin inactivation enzyme 15-hydroxyprostaglandin dehydrogenase. Using pharmacological inhibitors and knockout models of the pro-resolution enzyme 15-lipoxygenase, we show that blocking the bioactive lipid class switching impairs myoblast differentiation in vitro and muscle regeneration in vivo. Administration of the pro-resolving mediator Protectin-D1 restores myogenesis, enhances muscle regeneration post-injury and improves muscle phenotype in a dystrophic mouse model. Overall, these findings provide a better comprehension of the mechanisms regulating myogenic progression, which opens new therapeutic avenues for muscle regeneration and dystrophies.