Cytokines

Key Biological Properties: Endoglin is a transmembrane glycoprotein with a large extracellular domain, a hydrophobic transmembrane domain, and a short cytoplasmic tail . It exists in two isoforms, L-endoglin and S-endoglin, created by alternative splicing .

Expression Patterns: Endoglin expression is usually low in resting endothelial cells but increases significantly during neoangiogenesis, inflammation, and tissue repair . It is highly expressed in vascular endothelial cells, activated macrophages, and fibroblasts .

Tissue Distribution: Endoglin is found in all tissues with endothelial cells, particularly in tumor vessels, inflamed tissues, and during embryogenesis . It is also present in monocytes, vascular smooth muscle cells, and tissues undergoing fibrosis .

Primary Biological Functions: Endoglin is essential for angiogenesis, the process of new blood vessel formation . It acts as a co-receptor for TGF-β family ligands, modulating cellular responses to these growth factors .

Role in Immune Responses and Pathogen Recognition: Endoglin plays a role in leukocyte trafficking and extravasation by binding to leukocyte integrins . It is involved in the immune response by regulating the adhesion and migration of immune cells .

Mechanisms with Other Molecules and Cells: Endoglin interacts with various molecules, including TGF-β receptors, integrins, and metalloproteinases . It can be cleaved by metalloproteinase MMP-14, producing a soluble form that acts as a ligand trap .

Binding Partners and Downstream Signaling Cascades: Endoglin binds to TGF-β1, TGF-β3, BMP-2, BMP-7, and BMP-9, modulating their signaling pathways . It also interacts with zyxin, ZRP-1, beta-arrestin, and Tctex2beta, influencing cytoskeletal dynamics and cell migration .

Control of Expression and Activity: Endoglin expression is regulated by hypoxia, oxidative stress, and signaling molecules like TGF-β1 and BMP-9 . Its activity is modulated by post-translational modifications, including phosphorylation and cleavage by metalloproteinases .

Transcriptional Regulation and Post-Translational Modifications: Endoglin expression is upregulated by transcription factors such as Fli-1 and Erg . Post-translational modifications, including glycosylation and phosphorylation, affect its stability and function .

Biomedical Research: Endoglin is a marker for angiogenesis and is used in research on vascular diseases and cancer .

Diagnostic Tools: Elevated endoglin levels are associated with tumor angiogenesis, making it a potential diagnostic marker for cancer .

Therapeutic Strategies: Targeting endoglin with antibodies or inhibitors is being explored as a therapeutic strategy for cancer and other angiogenesis-related diseases .

Development: Endoglin is crucial for cardiovascular development and vascular remodeling during embryogenesis .

Aging and Disease: Endoglin expression is associated with various diseases, including hereditary hemorrhagic telangiectasia (HHT), preeclampsia, and cancer . Its role in angiogenesis and immune responses makes it a key player in aging and disease progression .