Regulation of brain endothelial cell physiology by the TAM receptor tyrosine kinase Mer
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ABSTRACT: The receptor tyrosine kinase Mer (gene name Mertk) acts in vascular endothelial cells (ECs) to tighten the blood-brain barrier (BBB) subsequent to viral infection. Correspondingly, we found that Mer regulates the expression and activity of a large cohort of cytoskeletal and BBB proteins, together with endothelial nitric oxide synthase, in brain ECs. We further found that Mer controls the expression of multiple angiogenic genes, and that EC-specific Mertk gene inactivation results in perturbed vascular sprouting and a compromised BBB after induced photothrombotic stroke. Unexpectedly, stroke lesions in the brain were also markedly reduced in the absence of EC Mer, which was linked to reduced plasma expression of fibrinogen, prothrombin, and other effectors of blood coagulation. Together, these results demonstrate that Mer is a central regulator of angiogenesis, BBB integrity, and blood coagulation in the mature vasculature. They may also account for disease severity following infection with the coronavirus SARS-CoV-2.
INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Fusion Lumos
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: Greg Lemke
PROVIDER: MSV000091355 | MassIVE | Thu Feb 23 23:12:00 GMT 2023
REPOSITORIES: MassIVE
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