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

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.

Computational Investigation of Cell Migration Behavior in a Confluent Epithelial Monolayer

Cell migration plays a significant role in many biological activities,yet the physical mechanisms of cell migration are still not well understood.In this study,a continuum physics-based epithelial monolayer model including the intercellular interaction was employed to study the cell migration behavior in a confluent epithelial monolayer at constant cell density.The epithelial cell was modeled as isotropic elastic material.Through finite element simulation,the results revealed that themotile cellwas subjected to higher stress than the other jammed cells during the migration process.Cell stiffness was implied to play a significant role in epithelial cell migration behavior.Higher stiffness results in smaller displacement and lower migration speed.