Endothelial cell-cell adhesion and signaling

Abstract

Endothelial cells line blood vessels and provide a dynamic interface between the blood and tissues. They remodel to allow leukocytes, fluid and small molecules to enter tissues during inflammation and infections. Here we compare the signaling networks that contribute to endothelial permeability and leukocyte transendothelial migration, focusing particularly on signals mediated by small GTPases that regulate cell adhesion and the actin cytoskeleton. Rho and Rap GTPase signaling is important for both processes, but they differ in that signals are activated locally under leukocytes, whereas endothelial permeability is a wider event that affects the whole cell. Some molecules play a unique role in one of the two processes, and could therefore be targeted to selectively alter either endothelial permeability or leukocyte transendothelial migration.

Silica nanomaterials induce organ injuries by Ca2+-ROS-initiated disruption of the endothelial barrier and triggering intravascular coagulation

“…Results from the applications of pharmacological tools, including YM58483 (CRAC channel blocker), NAC (ROS scavenger), and PP1 (Src tyrosine kinase inhibitor), supported the proposed signaling pathway. Other studies also support this pathway although alternative nanomaterials and experimental designs were used [15,17,38,39].…”

“…F-actin is a major actin protein in the endothelium and it is remodeled in response to nanomaterial exposure, oxidative stress and tumor necrosis factor [15,36,37]. Actin is an important component of "stress fibers" [38] and is responsible for endothelial contraction, which may lead to widening of inter-endothelial junctional gap and failure of the endothelial barrier [39]. F-actin remodeling may also suppress endothelial migration and tube formation and further disrupt the endothelial barrier.…”

Septin Roles and Mechanisms in Organization of Endothelial Cell Junctions

“…We found previously that septins are required for the proper organization of VEcadherin at cell junctions of microvascular endothelial monolayers composed of human primary endothelial cells by observing that loss of septin 2 disrupted VE-cadherin structure, membrane dynamics, and junctional integrity 20 . The junctional integrity of the endothelial monolayer is tightly regulated by a number of diverse intercellular adhesion proteins at cellcell contact sites in response to cellular and molecular stimuli 69 . In this study, we extended our analysis by asking whether septin 2 is required to regulate the organization of other adhesion and junctional proteins, including nectin-2, afadin, PECAM-1 and ZO-1.…”

GDNF enhances human blood-nerve barrier functionin vitrovia MAPK signaling pathways

“…This study supports prior in vitro human BNB observations and demonstrates that restrictive barrier function does not simplistically involve upregulation of specific adherens and tight junction proteins alone, but critically involves early cytoskeletal changes required to provide the scaffolding needed for restrictive intercellular junctional complex formation. [32][33][34][35][36] Due to phenotypic and functional Figure 10. Effect of GDNF on selected human BNB junctional complex proteins following serum withdrawal.…”