PIEZO1 Channels Modulate the Small Extracellular Vesicle Release in C2C12 Cells

Area of Science:

• Cell Biology
• Muscle Physiology
• Extracellular Vesicles

Background:

• PIEZO1 channels are mechanosensitive ion channels crucial for cell function.
• Their role in skeletal muscle regeneration is recognized, but mechanisms are unclear.
• Small extracellular vesicles mediate intercellular communication vital for tissue repair.

Purpose of the Study:

• To investigate PIEZO1's influence on small extracellular vesicle release in myogenic C2C12 cells.
• To characterize the effects of PIEZO1 activation on vesicle content and function.
• To explore PIEZO1's role in skeletal muscle precursor cell communication.

Main Methods:

• Treatment of myoblasts and myotubes with the PIEZO1 agonist Yoda1.
• Isolation and characterization of released small extracellular vesicles via ultracentrifugation, Western blotting, Nano Tracking, and proteomic analysis.
• Assessment of vesicle-mediated effects on myotube formation.

Main Results:

• Yoda1 treatment significantly increased small extracellular vesicle release and altered proteomic cargo in myotubes, but not myoblasts.
• Small extracellular vesicles from Yoda1-treated cells promoted myotube formation with differing capacities.
• PIEZO1 expression in vesicles increased in myotubes, suggesting cell-type-specific biogenesis.

Conclusions:

• PIEZO1 activation controls small extracellular vesicle release and cargo in myogenic precursors.
• PIEZO1 plays a significant role in skeletal muscle regeneration via extracellular vesicle-mediated communication.
• Findings elucidate PIEZO1's function in skeletal muscle physiopathology.