The goal of Project 1 is to define the function of the recently identified albumin-binding 60 kDa glycoprotein (gp60) on the endothelial cell surface in mediating increased vascular endothelial permeability. We have purified gp60 from bovine pulmonary microvessel endothelial cell (BPMVEC) membranes and human lung tissue. Cross-linking of gp60 using an anti-gp60 antibody (Ab) and secondary Ab increased the uptake and transport of 125 I-labeled albumin 2- to 3-fold without an increase in liquid permeability. Studies have co-localized gp60 with caveolin-surface gp60 with its ligand, albumin, stimulated the internalization of gp60 in caveolae. These results have led to the hypothesis that albumin-binding to the endothelial cell surface gp60 mediates the internalization and transcytosis of albumin. Project 1 will (1) identify the albumin binding domains of gp60 and their amino acid sequences; (2) determine the in vitro and in vivo effects of gp60 activation on the endothelial barrier function; (3) study the interactions of gp60 with caveolin-1 and members of Src tyrosine kinases and determine the G-protein transduction pathways intervening between albumin binding and the membrane dynamics that regulate endothelial permeability; (4) determine the function of gp60 in mediating albumin permeability by cloning gp60 and studying its expression; and (5) determine the role of gp60 in mediating states of increased pulmonary vascular endothelial permeability. With the achievement of these aims, we will provide new insights into the role of gp60 in regulating endothelial permeability via the transcellular pathway.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL060678-02
Application #
6418803
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2001-03-01
Project End
2002-02-28
Budget Start
Budget End
Support Year
2
Fiscal Year
2001
Total Cost
$266,534
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Marsboom, Glenn; Rehman, Jalees (2018) Hypoxia Signaling in Vascular Homeostasis. Physiology (Bethesda) 33:328-337
Lv, Yang; Kim, Kyungho; Sheng, Yue et al. (2018) YAP Controls Endothelial Activation and Vascular Inflammation Through TRAF6. Circ Res 123:43-56
Christoforidis, Theodore; Driver, Tom G; Rehman, Jalees et al. (2018) Generation of controllable gaseous H2S concentrations using microfluidics. RSC Adv 8:4078-4083
Di, Anke; Xiong, Shiqin; Ye, Zhiming et al. (2018) The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation. Immunity 49:56-65.e4
Chen, Zhenlong; D S Oliveira, Suellen; Zimnicka, Adriana M et al. (2018) Reciprocal regulation of eNOS and caveolin-1 functions in endothelial cells. Mol Biol Cell 29:1190-1202
Le Master, Elizabeth; Huang, Ru-Ting; Zhang, Chongxu et al. (2018) Proatherogenic Flow Increases Endothelial Stiffness via Enhanced CD36-Mediated Uptake of Oxidized Low-Density Lipoproteins. Arterioscler Thromb Vasc Biol 38:64-75
Potje, Simone R; Chen, Zhenlong; Oliveira, Suellen D'Arc S et al. (2017) Nitric oxide donor [Ru(terpy)(bdq)NO]3+ induces uncoupling and phosphorylation of endothelial nitric oxide synthase promoting oxidant production. Free Radic Biol Med 112:587-596
Tsang, Kit Man; Hyun, James S; Cheng, Kwong Tai et al. (2017) Embryonic Stem Cell Differentiation to Functional Arterial Endothelial Cells through Sequential Activation of ETV2 and NOTCH1 Signaling by HIF1?. Stem Cell Reports 9:796-806
Marsboom, Glenn; Chen, Zhenlong; Yuan, Yang et al. (2017) Aberrant caveolin-1-mediated Smad signaling and proliferation identified by analysis of adenine 474 deletion mutation (c.474delA) in patient fibroblasts: a new perspective on the mechanism of pulmonary hypertension. Mol Biol Cell 28:1177-1185
Andresen Eguiluz, Roberto C; Kaylan, Kerim B; Underhill, Gregory H et al. (2017) Substrate stiffness and VE-cadherin mechano-transduction coordinate to regulate endothelial monolayer integrity. Biomaterials 140:45-57

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