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
Related in: MedlinePlus
Mentions: Agonist-induced activation of Rac1 protects the vascular endothelial barrier in thrombin-stimulated ECs by inhibiting the thrombin-induced Rho pathway of barrier dysfunction (Finigan et al., 2005; Birukova et al., 2007c; Tauseef et al., 2008; Baumer et al., 2009). Involvement of Asef in HGF-induced barrier protective effects against thrombin was tested in control and Asef-depleted cells. Agonist-induced permeability responses in control cells treated with nonspecific RNA and Asef-depleted EC monolayers were monitored by TER measurements. HGF exhibited a prominent protective effect against thrombin-induced TER decline in EC monolayers treated with nonspecific RNA (Figure 7A, left). In contrast, Asef knockdown impaired HGF-induced EC barrier protection against thrombin (Figure 7A, right). Effects of Asef knockdown on agonist-induced TER changes are summarized in the bar graph in Figure 7A (bottom).
Affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.