Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury  

作　　者：Jiewen Chen Xiaolin Zeng Le Wang Wenwu Zhang Gang Li Xing Cheng Peiqiang Su Yong Wan Xiang Li 

机构地区：[1]Department of Spine Surgery,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong Province,China [2]Guangdong Province Key Laboratory of Orthopedics and Traumatology,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2025年第2期557-573,共17页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China, Nos.81971151 (to YW), 82102528 (to XL), 82102583 (to LW);the Natural Science Foundation of Guangdong Province, China, Nos.2020A1515010265 (to YW), 2020A1515110679 (to XL), and 2021A1515010358 (to XL)

摘　　要：Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

关 键 词：ASTROCYTES AXL cell polarization GAS6 Hippo signal inflammatory micro-environment intercellular interaction MICROGLIA single-cell sequencing spinal cord injury 

分 类 号：R651.2[医药卫生—外科学]