After Traumatic Brain Injury, EPHA4 Enhances Endoplasmic Reticulum Stress to Promote M1 Microglial Polarization Through the MAPK Signaling Pathway
Yang Tan, Jing Xia, Mingwei Liu, Sangyang Deng, Haiying Wu, Chuanyun Qian
TL;DR
This study shows that EPHA4 promotes harmful microglial activity after brain injury by increasing stress signals, suggesting a new target for treatment.
Contribution
The novel finding is that EPHA4 drives M1 microglial polarization through endoplasmic reticulum stress and MAPK signaling in traumatic brain injury.
Findings
EPHA4 expression is upregulated in TBI rat brain tissue.
KYL peptide reduces M1 polarization and proinflammatory cytokines.
EPHA4 activates MAPK signaling to enhance endoplasmic reticulum stress and M1 polarization.
Abstract
Traumatic brain injury (TBI) is an important cause of disability and death worldwide. The development of neuroinflammation after TBI is related to the brain parenchyma. M1‐type microglia play important roles in this process, but the specific mechanism through which regulating microglia M1 polarization is still not fully understood. This study aimed to investigate the role of ephrin receptor A4 (EPHA4) in the M1 polarization of microglia after TBI. A TBI rat model was established by the controlled cortical impact (CCI) method, and M1 polarization of GMI‐R1 cells was induced by lipopolysaccharide (LPS) treatment. Target genes associated with the progression of TBI were screened by transcriptome sequencing; the expression of key genes and proteins was detected by real‐time quantitative PCR (RT‒qPCR), Western blot, ELISA, and immunofluorescence, and the damage of the rat brain tissue and…
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Taxonomy
TopicsAxon Guidance and Neuronal Signaling · Neuroinflammation and Neurodegeneration Mechanisms · Barrier Structure and Function Studies