Astrocyte-conditional knockout of MOB2 inhibits the phenotypic conversion of reactive astrocytes from A1 to A2 following spinal cord injury in mice

Abstract

After spinal cord injury (SCI), reactive astrocytes in the injured area are triggered after spinal cord injury (SCI) and to polarize into A1 astrocytes with a proinflammatory phenotype or A2 astrocytes with an anti-inflammatory phenotype. Monopolar spindle binder 2 (MOB2) induces astrocyte stellation, maintains cell homeostasis, and promotes neurite outgrowth; however, its role in the phenotypic transformation of reactive astrocytes remains unclear. Here, we confirmed for the first time that MOB2 is associated with A1/A2 phenotypic switching in reactive astrocytes following SCI in mice. MOB2 modulated A1/A2 transformation in a primary astrocyte reactive cell model. Therefore, we constructed MOB2 conditional knockout mice (MOB2^GFAP-CKO) and discovered that conditional knockout of MOB2 inhibited the conversion of reactive astrocytes from A1 to A2 and hindered spinal cord function recovery. Mechanistically, MOB2 increased the activation of PI3K-AKT signaling to promote A1/A2 transformation in vitro, whereas sc79 (an AKT activator) reversed the subtype transformation of reactive astrocytes and improved functional recovery in MOB2GFAP-CKO mice after SCI. Taken together, study provides the first insights into how MOB2 acts as a novel regulator to promote the conversion this of the reactive astrocyte phenotype from A1 to A2, showing great potential for the treatment of SCI.

Keywords: MOB2; PI3K-AKT signaling; Spinal cord injury.