Hb-EGF directs systemic muscle repair.

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.