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Updated: Aug 22, 2025

Analyzing Satellite Cell Function During Skeletal Muscle Regeneration by Cardiotoxin Injury and Injection of Self-delivering siRNA In Vivo
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Analyzing Satellite Cell Function During Skeletal Muscle Regeneration by Cardiotoxin Injury and Injection of Self-delivering siRNA In Vivo

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Cilia-Mediated Insulin/Akt and ST2/JNK Signaling Pathways Regulate the Recovery of Muscle Injury

Daishi Yamakawa1, Junya Tsuboi2,3, Kousuke Kasahara1

  • 1Department of Physiology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 14, 2022
PubMed

Insights

Primary cilia regulate fibro/adipogenic progenitors (FAPs) during muscle regeneration. Elongated cilia promote repair by inhibiting fat accumulation and enhancing IL-13 production via specific signaling pathways.

Area of Science:

  • Muscle regeneration and repair
  • Cellular signaling pathways
  • Adipogenesis and skeletal muscle biology

Background:

  • Skeletal muscle regeneration is complex, with fibro/adipogenic progenitors (FAPs) playing a key role.
  • Fatty tissue accumulation can impair muscle function in aging and disease.
  • The influence of primary cilia on FAP behavior during muscle repair was previously unknown.

Purpose of the Study:

  • To investigate the role of primary cilia in regulating FAPs during skeletal muscle regeneration.
  • To determine how genetic manipulation of ciliary regulators affects FAP function and muscle repair outcomes.

Main Methods:

  • Genetic ablation of trichoplein (TCHP), a ciliary regulator, in mice.
  • Analysis of FAP behavior, adipogenic differentiation, and muscle regeneration post-injury.
  • Investigation of cilia-dependent signaling pathways, including insulin/Akt and IL-33/ST2/JNK.

Main Results:

  • Genetic ablation of TCHP led to ciliary elongation in FAPs after injury.
  • Elongated cilia promoted muscle regeneration while inhibiting FAP adipogenesis.
  • Defective adipogenesis was linked to impaired cilia-dependent lipid raft dynamics and insulin/Akt signaling.
  • Intramuscular FAPs produced increased interleukin-13 (IL-13) upon ciliary elongation.
  • Long cilia activated the IL-33/ST2/JNK axis, enhancing IL-13 production, myoblast proliferation, and M2 macrophage polarization.

Conclusions:

  • Fibro/adipogenic progenitors (FAPs) orchestrate skeletal muscle regenerative responses through primary cilia.
  • Cilia-mediated insulin/Akt signaling regulates adipogenesis, while cilia-mediated ST2/JNK signaling modulates IL-13 production.
  • Targeting primary cilia in FAPs offers a potential therapeutic strategy for enhancing muscle regeneration and preventing fat accumulation.
Keywords:
adipogenesisfibro/adipogenic progenitorsinterleukin 13interleukin 33lipid raftprimary ciliaskeletal muscle regeneration

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