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PIEZO1 Channels Modulate the Small Extracellular Vesicle Release in C2C12 Cells

Title: PIEZO1 Channels Modulate the Small Extracellular Vesicle Release in C2C12 Cells
Authors: Bernareggi Annalisa; Zhang Wen Ru; Sanchez‐Sanchez Laura; Norbedo Alessia; Fracassi Anna; Lucafò Marianna; Sciancalepore Marina; Alberto Griffoni; Russell K. William; Taglialatela Giulio; Lorenzon Paola; Limon Agenor
Contributors: Bernareggi, Annalisa; Zhang Wen Ru; Laura, Sanchez‐sanchez; Norbedo, Alessia; Anna, Fracassi; Lucafò, Marianna; Sciancalepore, Marina; Griffoni, Alberto; William, Russell K.; Giulio, Taglialatela; Lorenzon, Paola; Limon, Agenor
Publication Year: 2026
Collection: Università degli studi di Trieste: ArTS (Archivio della ricerca di Trieste)
Subject Terms: C2C12; PIEZO1; Yoda1; extracellular vesicle; muscle regeneration; myogenic precursor; myotubes
Description: PIEZO1 are mechanically-activated ion channels expressed in many cell types. Their pharmacological activation by the selective agonist Yoda1 has been reported to favor skeletal muscle regeneration by controlling the fate of myogenic precursors cells, but the underlying mechanisms remain largely unknown. Hereby, we investigated the possibility that PIEZO1 could control the release of small extracellular vesicles in myogenic C2C12 cells. Myoblasts and differentiated myotubes were treated with the PIEZO1 agonist Yoda1 (5 μM) for 24 hours. Released small extracellular vesicles were isolated by ultracentrifugation methods, and characterized by Western blotting, Nano Tracking and proteomic analysis. Pharmacological activation of PIEZO1 showed cell-type-specific effects: In myoblasts, Yoda1 treatment did not significantly affect the size or release of the small extracellular vesicles and resulted in only minor alterations to their proteomic profile. In myotubes Yoda1 treatment significantly increased small extracellular vesicles release and caused subtsantial alterations to the proteomic cargo. Notably, small extracellular vesicles released from both myoblasts and myotubes under PIEZO1 activation promoted myotube formation, though they did so through different capacities. Interestingly, in myotubes, Yoda1 also increased the expression of PIEZO1 protein of the vesicles suggesting a different biogenesis in undifferentiated and differentiated myogenic cells. Here, we propose PIEZO1 as a key element in controlling the release of small extracellular vesicles in myogenic precursors. Given the critical role of small extracellular vesicles in intercellular communication during muscle regeneration, our findings contribute to a better understanding of the role of PIEZO1 in the physiopathology of skeletal muscle tissue.
Document Type: article in journal/newspaper
File Description: ELETTRONICO
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/41834672; volume:241; issue:3; firstpage:"-"; lastpage:"-"; numberofpages:11; journal:JOURNAL OF CELLULAR PHYSIOLOGY; https://hdl.handle.net/11368/3128399
DOI: 10.1002/jcp.70155
Availability: https://hdl.handle.net/11368/3128399; https://doi.org/10.1002/jcp.70155; https://onlinelibrary.wiley.com/doi/10.1002/jcp.70155
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.A1284514
Database: BASE