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

Xin Tao; Haining Chen; Zhenghuan Zhu; Tianran Ren; Hongming Zhen; Xiaoliang Sun; Yu Song; Xu Xu; Zhiwen Song; Jinbo Liu

doi:10.1016/j.ijbiomac.2025.140289

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

Int J Biol Macromol. 2025 Jan 23:300:140289. doi: 10.1016/j.ijbiomac.2025.140289. Online ahead of print.

Authors

Xin Tao¹, Haining Chen², Zhenghuan Zhu³, Tianran Ren⁴, Hongming Zhen⁴, Xiaoliang Sun³, Yu Song⁴, Xu Xu⁴, Zhiwen Song⁵, Jinbo Liu⁶

Affiliations

¹ Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, People's Republic of China; Department of Orthopedics, The People's Hospital of Liyang, Liyang 213300, Jiangsu, People's Republic of China.
² Department of Orthopedics, The First Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu, People's Republic of China.
³ Department of Orthopedics, Changzhou Maternal and Child Health Care Hospital, Changzhou 213000, Jiangsu, People's Republic of China.
⁴ Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, People's Republic of China.
⁵ Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, People's Republic of China. Electronic address: realszw@126.com.
⁶ Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, People's Republic of China. Electronic address: czljbljb@126.com.

PMID: 39863205
DOI: 10.1016/j.ijbiomac.2025.140289

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.