establishment of endothelial barrier

Definition

Target type: biologicalprocess

The establishment of a barrier between endothelial cell layers, such as those in the brain, lung or intestine, to exert specific and selective control over the passage of water and solutes, thus allowing formation and maintenance of compartments that differ in fluid and solute composition. [GOC:dph]

The establishment of an endothelial barrier, a critical component of the vascular system, is a complex and tightly regulated process that involves intricate cellular interactions and signaling pathways. It begins with the differentiation of endothelial cells (ECs) from progenitor cells, followed by their migration and proliferation, leading to the formation of a nascent vascular network. Once ECs align and form a continuous monolayer, they initiate the formation of intercellular junctions, primarily tight junctions (TJs) and adherens junctions (AJs). These junctions serve as physical barriers, preventing the passage of macromolecules and maintaining vascular integrity.

The formation of TJs involves the interaction of transmembrane proteins, such as claudins, occludins, and junctional adhesion molecules (JAMs), which associate with intracellular adapter proteins, including ZO-1, ZO-2, and ZO-3. These proteins interact with the actin cytoskeleton, providing structural support and regulating TJ permeability. AJs are primarily composed of cadherins, transmembrane proteins that bind to β-catenin and α-catenin on the intracellular side. These proteins, in turn, interact with the actin cytoskeleton, contributing to cell adhesion and barrier integrity.

The formation and maintenance of the endothelial barrier are influenced by various signaling pathways, including VEGF (vascular endothelial growth factor), TGF-β (transforming growth factor beta), and Wnt signaling pathways. These pathways regulate the expression and localization of junctional proteins, as well as the organization of the actin cytoskeleton, ultimately affecting barrier function.

Additionally, ECs express and respond to various soluble factors and mechanical stimuli, such as shear stress, that further contribute to barrier formation and maintenance. For example, shear stress promotes the activation of downstream signaling pathways, leading to the phosphorylation and stabilization of junctional proteins, strengthening the barrier.

The endothelial barrier is not static but rather a dynamic structure that can be modulated in response to various physiological and pathological stimuli. This dynamic nature allows for the adaptation of the barrier to changing conditions, such as during inflammation, angiogenesis, or tumor growth.

In conclusion, the establishment of an endothelial barrier is a complex process involving multiple cellular and molecular events that contribute to the formation and maintenance of a functional vascular network. This process is tightly regulated by various signaling pathways and external stimuli, ensuring the integrity of the barrier and the efficient transport of nutrients and oxygen throughout the body.'
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Proteins (10)

Compounds (804)