Early exercise disrupts a pro-repair extracellular matrix program during zebrafish fin regeneration

Area of Science:

• Regenerative Biology
• Mechanobiology
• Developmental Biology

Background:

• Mechanical stimulation from exercise influences cellular responses during tissue repair.
• Understanding exercise impacts on tissue regeneration can enhance therapeutic strategies.
• Zebrafish caudal fin regeneration is a robust model for studying tissue repair.

Purpose of the Study:

• To investigate the impact of exercise timing on zebrafish fin regeneration.
• To elucidate the cellular and molecular mechanisms underlying exercise-induced effects on regeneration.
• To explore the role of extracellular matrix (ECM) and mechanotransduction in exercise-modulated regeneration.

Main Methods:

• Zebrafish caudal fin regeneration model.
• Swim tunnel for controlled exercise intervention.
• Long-term tracking of fluorescently labeled cell lineages.
• Transcriptomic profiling and section staining.
• Hyaluronic acid (HA) synthesis inhibition and depletion.
• Analysis of Yes-associated protein (Yap) localization and cell proliferation.

Main Results:

• Exercise initiated during, but not after, blastema establishment impaired fin regeneration.
• Exercise disrupted blastemal mesenchyme formation and reduced extracellular matrix (ECM) gene expression, including hyaluronic acid (HA) synthesis.
• HA depletion mimicked exercise effects, disrupting blastema formation.
• Exercise and reduced HA decreased nuclear Yap localization and cell proliferation.
• HA density correlated with nuclear Yap, suggesting a role in mechanotransduction.

Conclusions:

• Early exercise during fin regeneration disrupts an HA-rich ECM that supports blastema expansion.
• These findings highlight the interplay between mechanotransduction and ECM in regeneration.
• The timing of exercise interventions is critical for regenerative therapies and rehabilitation.