Inactivation of Gas6/Axl signaling aggravates microglia-astrocyte cross 1 polarization in spinal cord injury
Inactivation of Gas6/Axl signaling aggravates microglia-astrocyte cross 1 polarization in spinal cord injury
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DOI：
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发表时间：
2023
影响因子：
6.1
通讯作者：
Xiang Li
中科院分区：
文献类型：
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作者：
Jiewen Chen;Xiaolin Zeng;Le Wang;Wenwu Zhang;Gang Li;Xing Cheng;Peiqiang Su;Yong Wan;Xiang Li
In spinal cord injury (SCI), severe inflammatory response and scar formation at the site of injury impede neural tissue repair, which have been shown to be induced by pro-inflammatory microglia and cytotoxic astrocytes. In this study, we found a cross-polarization between pro-inflammatory microglia and cytotoxic astrocytes: in the SCI region, pro-inflammatory microglia (MG1 and MG3) induced naive astrocytes to polarize into a cytotoxic phenotype. In response, cytotoxic astrocytes reciprocally polarized microglia (MG0) to a pro-inflammatory phenotype (MG1 and MG3), which could further polarize cytotoxic astrocytes. Furthermore, this cross-polarization was attributed to the downregulation of growth arrest-specific 6 (Gas6) and its receptor Axl in microglia and astrocytes. Excitingly, we observed that tissue repair and locomotor recovery of the injured spinal cord were facilitated after intrathecal injection of Gas6 in the rat model. Finally, this study revealed that Gas6 suppressed the polarization of pro-inflammatory microglia by inhibiting the NF-κB/p65 and JAK/Stat3 signaling pathway; and simultaneously suppressed the polarization of cytotoxic astrocytes by inhibiting the YES-associated protein signaling pathway. Taken together, these findings indicate that the absence of Gas6 initiates the cross-polarization between pro-inflammatory microglia and cytotoxic astrocytes in SCI, which induces severe inflammation and scar formation that impede neural tissue repair, and unravels the potential of Gas6 in SCI treatment
