Inactivation of Gas6/Axl signaling aggravated Microglia-Astrocyte cross regulation after spinal cord injury
Aggressive inflammation and excessive scar formation are the main cause to the difficulty of neural tissue repair after spinal cord injury (SCI). Microglia and astrocytes act as important role in this micro-environment of SCI and there is cross regulation between microglia and astrocytes. After SCI, MG0 polarized into MG1 and MG3 which were belong to pro-inflammatory phenotype microglia; Naive astrocytes polarized into Reactive and Scar-forming astrocytes. Growth arrest-specific 6 (Gas6) and its receptor Axl was declined in all these cells after SCI. In vitro study, Gas6 had the negative effect on cytotoxic astrocytes and pro-inflammatory microglia polarization and even the cross regulation between cytotoxic astrocytes and pro-inflammatory microglia. Further mechanism study indicated that Gas6 suppressed cytotoxic phenotype polarization of astrocytes through inhibited the activation of YES-associated protein (YAP) signal pathway and suppressed pro-inflammatory phenotype polarization of microglia through inhibited the activation of NF-?B/p65 and JAK/Stat3 signal pathways. In vivo study, Gas6 treatment suppressed cytotoxic astrocytes and pro-inflammatory microglia polarization at the injured site of spinal cord to facilitate tissue repair and loco-motor recovery. Overall design: Spinal cord damage can lead to sensory, motor, and autonomic dysfunction distal to the site of injury. The lack of effective treatment measures and the poor prognosis after injury are heavy burdens to patients and their families and greatly endanger human health. After spinal cord injury, the microenvironment localized to the injury is dramatically altered. The purpose of this RNA-seq analysis was to examine the differences in the transcriptomes of normal wild-type mice and mice with spinal cord injury. Total RNA was purified from the spinal cord injury center, and differential expression analysis was performed to compare the transcriptomes of spinal cord injured mice with those of wild-type mice (Sham group, n=3 and SCI group, n=3).