Please use this identifier to cite or link to this item:
|Title:||Lung endothelial barrier disruption in Lyl1-deficient mice||Authors:||Pirot, Nelly
|Affiliations:||Department of Medical Laboratory Sciences||Keywords:||lymphoblastic leukemia-derived sequence 1
|Issue Date:||2014||Part of:||American journal of physiology-lung cellular and molecular physiology||Volume:||306||Issue:||8||Start page:||775||End page:||785||Abstract:||
Maturation of newly formed vessels is a multistep phenomenon during which functional endothelial barriers are established. Disruption of vessel integrity is an important feature in many physiological and pathological processes. We previously reported that lymphoblastic leukemia-derived sequence 1 (LYL1) is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. In this study, we show that LYL1 is also required during the formation of the mature endothelial barrier in the lungs of adult mice. Specifically, LYL1 knockdown in human endothelial cells downregulated the expression of ARHGAP21 and ARHGAP24, which encode two Rho GTPase-activating proteins, and this was correlated with increased RhoA activity and reorganization of the actin cytoskeleton into stress fibers. Importantly, in lungs of Lyl1-deficient mice, both vascular endothelial (VE)-cadherin and p120-catenin were poorly recruited to endothelial adherens junctions, indicative of defective cell-cell junctions. Consistent with this, higher Evans blue dye extravasation, edema, and leukocyte infiltration in the lung parenchyma of Lyl1−/− mice than in wild-type littermates confirmed that lung vascular permeability is constitutively elevated in Lyl1−/− adult mice. Our data show that LYL1 acts as a stabilizing signal for adherens junction formation by operating upstream of VE-cadherin and of the two GTPases Rap1 and RhoA. As increased vascular permeability is a key feature and a major mechanism of acute respiratory distress syndrome, molecules that regulate LYL1 activity could represent additional tools to modify the endothelial barrier permeability. The mature continuous vascular endothelium that lines blood vessels forms a selective and semipermeable barrier to control the exchange of solutes, proteins, fluids, and immune cells between blood and tissues. Fine regulation of endothelial permeability is required i.
|URI:||https://scholarhub.balamand.edu.lb/handle/uob/2216||DOI:||10.1152/ajplung.00200.2013||Open URL:||Link to full text||Type:||Journal Article|
|Appears in Collections:||Department of Medical Laboratory Sciences|
Show full item record
checked on Oct 23, 2021
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.