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  1. Home
  2. Sema4a Protects Against Muscle Atrophy And Promotes Repair By Regulating Intracellular Metabolic Signalling.
  1. Home
  2. Sema4a Protects Against Muscle Atrophy And Promotes Repair By Regulating Intracellular Metabolic Signalling.

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Sema4A Protects Against Muscle Atrophy and Promotes Repair by Regulating Intracellular Metabolic Signalling.

Caiyun Wang1,2, Honghong Chen2, Lingjie Shen3

  • 1Department of Orthopaedics, Mindong Hospital, Fujian Medical University, Fujian, China.

Journal of Cachexia, Sarcopenia and Muscle
|May 30, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

Semaphorin 4A (Sema4A) is identified as a key regulator in preventing muscle atrophy. Restoring Sema4A levels helps preserve muscle mass and function, offering a potential therapeutic strategy for muscle-wasting conditions.

Keywords:
FoxO3aPlexin B2Semaphorin 4Amuscle atrophymuscle repair

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Published on: September 18, 2019

Area of Science:

  • Muscle physiology and molecular biology
  • Immunology and cellular signaling
  • Therapeutic target identification

Background:

  • Skeletal muscle atrophy is a significant health concern linked to various diseases and treatments.
  • The molecular mechanisms preserving muscle integrity against atrophy triggers are not fully understood.
  • Semaphorin 4A (Sema4A), known for neural and immune roles, has an unexplored function in skeletal muscle.

Purpose of the Study:

  • To investigate the role of Semaphorin 4A (Sema4A) in skeletal muscle maintenance and atrophy.
  • To explore the therapeutic potential of Sema4A in mitigating muscle loss and promoting regeneration.
  • To elucidate the molecular pathways through which Sema4A exerts its effects on muscle tissue.

Main Methods:

  • Examined Sema4A expression in mouse models of muscle catabolism.
  • Utilized adeno-associated virus (AAV)-mediated Sema4A restoration in dexamethasone-induced atrophy and acute injury models.
  • Conducted mechanistic studies in C2C12 myotubes using gain- and loss-of-function approaches.
  • Main Results:

    • Sema4A expression is significantly downregulated in atrophic muscle conditions.
    • Sema4A restoration attenuated dexamethasone-induced muscle loss and accelerated functional recovery.
    • Sema4A signaling, via Plexin B2 (Plxnb2), suppressed FoxO3a nuclear translocation, inhibited atrogene expression, and reactivated the PI3K-AKT-mTOR anabolic pathway.
    • Sema4A promoted a reparative immune microenvironment, potentially modulated by Gdf15.

    Conclusions:

    • Sema4A acts as a novel protective regulator against skeletal muscle atrophy.
    • Sema4A mitigates muscle wasting by restoring anabolic signaling and fostering a proregenerative immune niche.
    • Sema4A represents a promising therapeutic target for muscle-wasting disorders.