Extracellular vesicles derived from astrocytes facilitated neurite elongation by activating the Hippo pathway

Abstract

Spinal cord injury (SCI) often causes severe neurological dysfunction, and facilitating neurite elongation is particularly important in its treatment. Astrocytes (AS) play an important role in the central nervous system (CNS), and their high plasticity and versatility provide a feasible entry point for relevant research. Our purpose was to explore whether extracellular vesicles (EVs) from astrocytes (AS-EVs) and lipopolysaccharide (LPS)-preactivated astrocytes (LPAS-EVs) facilitate neurite elongation, to explore the underlying mechanism, and to verify whether these EVs promote locomotor recovery in rats. We used LPS to preactivate astrocytes and cocultured them with PC12 cells to observe neurite changes, then extracted and identified AS-EVs and LPAS-EVs and the role and mechanism of these EVs in facilitating neurite elongation was examined in vivo and vitro. We demonstrated that AS-EVs and LPAS-EVs facilitated the elongation of neurites and the recovery of rats with SCI. LPAS-EVs had a stronger effect than AS-EVs, by activating the Hippo pathway, promoting monopole spindle binding protein 1 (MOB1) expression, and reducing Yes-associated protein (YAP) levels. The data also suggest a feedback regulation between MOB1 and p-YAP/YAP. In sum, AS-EVs and LPAS-EVs can play an active role in facilitating neurite elongation by activating the Hippo pathway. These findings provide a new strategy for treating SCI and other CNS-related injuries.

Keywords: Astrocytes; Extracellular vesicle; Hippo pathway; Neurite; SCI; YAP.