establishment of endothelial intestinal barrier

Definition

Target type: biologicalprocess

The establishment of a barrier between endothelial cell layers of the 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:krc, PMID:22155109]

The establishment of the endothelial intestinal barrier is a complex and multi-step process that involves the coordinated action of various cellular and molecular components. This barrier, also known as the intestinal microvascular barrier, serves as a selective gatekeeper, controlling the passage of nutrients, fluids, and immune cells between the intestinal lumen and the bloodstream.

Here is a detailed description of the key steps involved in the formation and maintenance of this crucial barrier:

**1. Angiogenesis and Endothelial Cell Differentiation:**

* The initial step involves the formation of new blood vessels, a process called angiogenesis. This is triggered by various growth factors and signaling molecules released by the surrounding tissues.
* As new blood vessels sprout, endothelial progenitor cells differentiate into mature endothelial cells, the specialized cells lining the inner surface of blood vessels.

**2. Tight Junction Formation:**

* Endothelial cells form tight junctions, specialized cell-cell junctions that seal the gaps between adjacent cells. This is a critical step in establishing a barrier that prevents leakage of blood components into the intestinal lumen.
* Tight junctions are composed of transmembrane proteins, such as claudins, occludin, and junctional adhesion molecules (JAMs), which interact with each other and with the cytoskeleton to create a tight seal.
* The expression and assembly of these junctional proteins are regulated by various signaling pathways, including the Rho/ROCK pathway, the VEGF pathway, and the Wnt pathway.

**3. Adherens Junction Formation:**

* Adherens junctions are another type of cell-cell junction that contributes to the structural integrity of the endothelial barrier. These junctions connect the cytoskeletons of adjacent cells, providing tensile strength and stability.
* Adherens junctions are primarily formed by the interaction of cadherin proteins, such as vascular endothelial cadherin (VE-cadherin), with the intracellular catenins.

**4. Basement Membrane Formation:**

* Endothelial cells are anchored to the underlying extracellular matrix (ECM) by a specialized structure called the basement membrane. This thin, sheet-like structure provides structural support and regulates cell adhesion and signaling.
* The basement membrane is primarily composed of type IV collagen, laminin, and other ECM components. Its formation involves the secretion of these molecules by endothelial cells and other cell types.

**5. Paracellular Transport Regulation:**

* The endothelial intestinal barrier is not impermeable; it allows controlled passage of molecules through the spaces between endothelial cells (paracellular pathway).
* The permeability of the paracellular pathway is regulated by the tight junctions. Different claudin isoforms, for example, can create pores with varying sizes, influencing the passage of specific molecules.
* Moreover, various signaling pathways, such as the inflammatory signaling pathways, can alter the permeability of the paracellular pathway, leading to increased leakage.

**6. Transcellular Transport Regulation:**

* In addition to paracellular transport, molecules can also cross the endothelial barrier through the cells themselves (transcellular pathway).
* Transcellular transport is mediated by specific transporters and receptors expressed on the endothelial cell surface. These proteins can facilitate the uptake and transport of nutrients, metabolites, and other molecules across the barrier.

**7. Immune Cell Recruitment and Response:**

* The endothelial intestinal barrier plays a crucial role in immune surveillance. It regulates the recruitment of immune cells from the bloodstream to the intestinal lumen.
* Endothelial cells express adhesion molecules, such as selectins and integrins, which bind to specific ligands on leukocytes, facilitating their attachment to the vessel wall.
* Upon activation, endothelial cells can also produce chemokines, which attract immune cells to the site of inflammation or infection.

**8. Maintenance and Remodeling:**

* The endothelial intestinal barrier is not static but is constantly being remodeled in response to various stimuli, including changes in nutrient availability, pathogen exposure, and inflammatory signals.
* Endothelial cells are capable of proliferation, migration, and apoptosis, allowing for dynamic adaptation of the barrier to maintain its integrity and function.

**9. Barrier Dysfunction and Disease:**

* Disruption of the endothelial intestinal barrier, often referred to as "barrier dysfunction," is a hallmark of several gastrointestinal diseases, including inflammatory bowel disease (IBD), celiac disease, and irritable bowel syndrome (IBS).
* Factors that can contribute to barrier dysfunction include infections, inflammation, autoimmune responses, and environmental toxins.
* Loss of barrier integrity can lead to increased intestinal permeability, allowing harmful substances to leak into the bloodstream, triggering immune responses and contributing to disease pathogenesis.

In summary, the establishment of the endothelial intestinal barrier is a tightly regulated process that involves numerous cellular and molecular components. This barrier plays a critical role in maintaining intestinal homeostasis and protecting the host from infection and inflammation. However, disruption of this barrier can contribute to the development and progression of various gastrointestinal diseases.

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