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Met/HGFR triggers detrimental reactive microglia in TBI
- Source :
- Cell reports 41(13), 111867 (2022). doi:10.1016/j.celrep.2022.111867, Cell Rep. 41:111867 (2022)
- Publication Year :
- 2022
-
Abstract
- The complexity of signaling events and cellular responses unfolding in neuronal, glial, and immune cells upon traumatic brain injury (TBI) constitutes an obstacle in elucidating pathophysiological links and targets for intervention. We use array phosphoproteomics in a murine mild blunt TBI to reconstruct the temporal dynamics of tyrosine-kinase signaling in TBI and then scrutinize the large-scale effects of perturbation of Met/HGFR, VEGFR1, and Btk signaling by small molecules. We show Met/HGFR as a selective modifier of early microglial response and that Met/HGFR blockade prevents the induction of microglial inflammatory mediators, of reactive microglia morphology, and TBI-associated responses in neurons and vasculature. Both acute and prolonged Met/HGFR inhibition ameliorate neuronal survival and motor recovery. Early elevation of HGF itself in the cerebrospinal fluid of TBI patients suggests that this mechanism has translational value in human subjects. Our findings identify Met/HGFR as a modulator of early neuroinflammation in TBI with promising translational potential. ispartof: Cell Reports vol:41 issue:13 ispartof: location:United States status: published
- Subjects :
- Neuroscience [CP]
phosphorylation
traumatic brain injury
HGFR
microglia
antibody array
General Biochemistry, Genetics and Molecular Biology
neuroinflammation
Mice, Inbred C57BL
VEGFR
Mice
Disease Models, Animal
Neuroscience
Hgfr
Met
Microglia
Neuroinflammation
Phosphorylation
Proteomics
Traumatic Brain Injury
Vegfr [Antibody Array
Btk
Cp]
proteomics
Brain Injuries, Traumatic
Humans
Animals
ddc:610
Signal Transduction
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 41
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Cell reports
- Accession number :
- edsair.doi.dedup.....81e5358dee54971d8c356706b73a2ea7