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: Exposure to TRAP6/HTV also significantly increased the total cell and neutrophil count in BAL samples in both Asef+/+ and Asef−/− mice as compared with the nonventilated controls (Figure 9A). Although we observed a trend toward higher levels of BAL cell count in TRAP6/HTV-treated Asef−/− mice, it did not reach statistical significance. By contrast, HGF administration before TRAP6/HTV caused significant reduction of cellular infiltration in Asef+/+ but not Asef−/− mice. TRAP6/HTV caused a significant increase in lung myeloperoxidase (MPO) activity compared with the control group (Figure 9B). HGF decreased MPO activity in the lungs of TRAP6/HTV-exposed Asef+/+ mice, whereas in Asef−/− mice, this effect was statistically insignificant.
Affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.