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    Skeletal muscle regeneration differs based on injury size. Large injuries activate a distinct repair program involving Heparin binding epidermal-like growth factor (Hb-EGF), unlike minor injuries, suggesting different regenerative pathways.

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    Area of Science:

    • Regenerative medicine
    • Zebrafish models
    • Skeletal muscle biology

    Background:

    • Regenerative capacity varies significantly across tissues, species, and life stages.
    • While minor skeletal muscle injuries regenerate well, extensive damage can lead to incomplete and debilitating repair.
    • The impact of injury magnitude on distinct regenerative programs remains underexplored.

    Purpose of the Study:

    • To investigate whether varying scales of muscle injury trigger different regenerative molecular programs.
    • To compare the molecular responses to systemic versus local muscle injuries in zebrafish.
    • To identify key molecular mediators specific to large-scale muscle regeneration.

    Main Methods:

    • Development of a systemic muscle injury model in zebrafish.
    • Transcriptomic analysis of both muscle and non-muscle tissues following injury.
    • Functional assessment of Heparin binding epidermal-like growth factor (Hb-EGF) in muscle repair.

    Main Results:

    • Systemic and local muscle injuries induce quantitatively and qualitatively distinct molecular responses.
    • Systemic muscle injury uniquely upregulates Heparin binding epidermal-like growth factor (Hb-EGF) expression in the epidermis.
    • Hb-EGF is essential for systemic muscle repair but not for local muscle repair.

    Conclusions:

    • Skeletal muscle employs distinct regenerative programs depending on the scale of injury.
    • Heparin binding epidermal-like growth factor (Hb-EGF) plays a critical role in systemic muscle repair following extensive injury.
    • These findings highlight the complexity of muscle regeneration and suggest therapeutic targets specific to injury severity.