Alix-mediated selective packaging of β-catenin into extracellular vesicles enhances their proangiogenic function

Le résumé fourni par la source

The function of extracellular vesicles (EVs) is determined by the molecular cargo they carry from their parent cells. Although apoptosis-linked gene 2-interacting protein X (Alix) is known to regulate EV cargo loading and functional properties, the specific mechanisms underlying its role in mediating β-catenin sorting and function remain unclear. In this study, we first observed the colocalization of Alix and β-catenin through immunofluorescence staining. To assess whether the interaction between Alix and β-catenin affects the function of mesenchymal stem cell (MSC)-derived EVs, we generated Alix-knockdown and Alix-overexpressing MSCs via viral transduction. Analysis of secreted EVs revealed that those derived from Alix-overexpressing MSCs promoted angiogenesis both in vitro and in a mouse model of hindlimb ischemia, whereas EVs from Alix-knockdown MSCs suppressed angiogenesis. Mechanistically, we confirmed that the Alix-β-catenin interaction selectively enhances β-catenin enrichment within EVs. In conclusion, our findings demonstrate that Alix plays a critical role in selectively packaging β-catenin into EVs, thereby enhancing their proangiogenic potency.

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