Asef controls vascular endothelial permeability and barrier recovery in the lung.
Bottom Line: Molecular inhibition of Asef attenuated HGF-induced peripheral accumulation of cortactin, formation of lamellipodia-like structures, and enhancement of VE-cadherin adherens junctions and compromised HGF-protective effect against thrombin-induced RhoA GTPase activation, Rho-dependent cytoskeleton remodeling, and EC permeability.This effect was lost in Asef(-/-) mice.This study shows for the first time the role of Asef in HGF-mediated protection against endothelial hyperpermeability and lung injury.
Affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.Show MeSH
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Mentions: VE-cadherin accumulation at the cell membrane compartment is essential for initiation adherens junction protein complex assembly. Using subcellular fractionation assay, we examined VE-cadherin membrane translocation in confluent (Figure 6A) and sparse (Figure 6B) EC cultures after HGF stimulation. HGF induced robust VE-cadherin membrane accumulation in dense (confluent) EC monolayers but not in sparse EC cultures. Observed VE-cadherin membrane accumulation was significantly attenuated in HGF-stimulated ECs with Asef knockdown. Immunofluorescence staining of VE-cadherin shows a dramatic increase of VE-cadherin–positive immunofluorescence signal at the cell junction area of HGF-stimulated EC monolayers. This effect was abolished by Asef knockdown (Figure 6C).
Affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.