Endomucin, also known as CD242 or MUC14, is a protein belonging to the mucin family. Mucins are characterized by heavy glycosylation, meaning they have many sugar molecules attached. Endomucin is a transmembrane glycoprotein, spanning the cell membrane with sugar chains extending from its surface. Its presence on cell surfaces suggests involvement in interactions between cells and their environment.
Cellular Presence
Endomucin is primarily located on endothelial cells, which form the inner lining of blood and lymphatic vessels. It is particularly abundant in the endothelial cells of capillaries and venules, but generally not found on most arterial endothelium. This distribution highlights its role in areas of fluid and cell exchange.
Endomucin is also present in the lymphatic sinus endothelium, but not in other lymphatic endothelial cells. Highly vascularized tissues like the heart, kidneys, and lungs show a rich presence. On the cell surface, endomucin is positioned at the apical side of the vascular endothelium, interacting directly with circulating cells and molecules.
Key Functions
Endomucin plays multiple roles in maintaining blood vessel health and stability. It is involved in angiogenesis, the formation of new blood vessels from existing ones. Endomucin influences endothelial cell migration, growth, and the formation of tube-like structures. It regulates the activity of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), a protein central to angiogenesis, by affecting its internalization and downstream signaling.
Endomucin also contributes to regulating immune cell adhesion and migration. It acts as an anti-adhesive molecule, preventing immune cells from sticking to healthy blood vessel walls. This anti-adhesive function helps prevent excessive inflammation by controlling how immune cells, such as neutrophils and monocytes, interact with the endothelium. Endomucin is a component of the endothelial glycocalyx, a protective, sugar-rich layer on the surface of endothelial cells. This glycocalyx maintains vascular integrity, regulates permeability, and influences interactions between cells and the extracellular matrix.
Role in Disease
Endomucin’s expression and function can change in various disease states. In inflammatory conditions, its levels on the cell surface can decrease, promoting immune cell adhesion and worsening inflammation. This downregulation by inflammatory factors like tumor necrosis factor-alpha (TNF-α) can lead to increased neutrophil infiltration into inflamed tissues. Overexpression of endomucin, however, can reduce inflammation and stabilize the blood-retinal barrier in conditions like diabetic retinopathy.
Endomucin also shows altered expression in certain types of cancer, suggesting a role in tumor development and spread. Its presence can increase when endothelial cells are stimulated by tumor-conditioned media or specific growth factors, hinting at its involvement in tumor angiogenesis, the formation of new blood vessels that supply tumors. Its influence on endothelial cell behavior, such as migration and proliferation, suggests it could promote tumor growth or metastasis. Endomucin’s dysregulation has been linked to vascular disorders, including atherosclerosis, where its fucosylation can accelerate the condition by promoting monocyte-endothelial adhesion. In kidney disease, the absence of endomucin has been shown to impair the structure and function of the glomerular filtration barrier, leading to increased inflammatory cell infiltration and albuminuria.