Met/HGFR triggers detrimental reactive microglia in TBI

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.

SEEK ID: http://localhost:3000/studies/76

Proteomics (Published)

Projects: Published Datasets

Study position:

help Creators and Submitter
Creator
Submitter
Activity

Views: 65

Created: 15th Oct 2024 at 14:08

help Tags

This item has not yet been tagged.

Powered by
(v.1.15.0)
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH