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Endoglin was initially identified on pre-B leukemia cells but has received most attention due to its high expression on activated endothelial cells. Transforming growth factor-β1 (TGF-β1) is a pleiotropic factor sensed by most cells. It regulates a broad spectrum of cellular responses including hematopoiesis. In order to process TGF-β1-responses in time and space in an appropriate manner, there is a tight regulation of its signaling at diverse steps. The downstream signaling is mediated by type I and type II receptors and modulated by the 'accessory' receptor Endoglin also termed cluster of differentiation 105 (CD105). In turn, Endoglin has been figured out as the causative factor for diseases associated with vascular dysfunction like hereditary hemorrhagic telangiectasia-1 (HHT-1), pre-eclampsia, and intrauterine growth restriction (IUPR). Aside the functional relevance of Endoglin in endothelial cells, CD105 is differentially expressed during hematopoiesis, arguing for a role of this receptor in the development of individual cell lineages.
Endoglin is a class I, single-membrane spanning receptor with an apparent molecular weight of 95 kDa containing a short cytoplasmic and a modular extracellular domain. This domain contains attachment sites for N- and O-dependent glycosylation and ligand binding residues. The homo-dimeric protein is stabilized by multiple intermolecular disulfide bridges. In case of Endoglin, defective N-glycosylation interferes with membrane localization similar to the transforming growth factor-β type II receptor (TβRII), as well as it impacts exosomal targeting of Endoglin. Direct binding of Endoglin to TGF-β is assumed to only occur in complex with the signaling receptors TGF-β type I and type II. The Endoglin C-terminus is a substrate for TGF-β-receptors, leading to serine/threonine phosphorylation, which regulates the interaction of Endoglin with those receptors. In addition, the C-terminal domain is tyrosine phosphorylated by Src kinase impacting Endoglin's trafficking and endothelial responses. In summary, the studies demonstrate that under physiological conditions (i) Endoglin is also functionally expressed outside ECs, (ii) Endoglin is a co-receptor primarily (but not exclusively) for ligands of the TGF-β-superfamily, and finally (iii) Endoglin not only impacts the function of cells expressing the receptor, but also acts in a paracrine manner.
Fig1. Endoglin biology in endothelial cells.
(Source: Int J Mol Sci, 2020)
Endoglin is highly expressed in active/angiogenic ECs. Therefore, dysfunction of this receptor affects several organ systems relying on angiogenesis. Such as the female reproductive system. IUPR is accompanied by placental hypoxia and increased TGF-β3 expression. Low oxygenation induces Endoglin expression mediated by TGF-β3. Aside ECs and trophoblasts, the expression of Endoglin was upregulated in decidua basalis of mid pregnancy in macrophages. In addition, endoglin affect vascular homeostasis, a more indirect role of Endoglin in ECs with respect to inflammation is its involvement in cell-cell contacts governing vessel architecture and the recruitment of immune cells (all lineages) from the circulation (extravasation). In turn, increased expression of Endoglin, which occurs for example in the autoimmune thyroiditis Graves' disease and psoriatic lesions, might lead to an enhanced inflammatory cell recruitment.
Fetal Hematopoiesis. It can be summarized that Endoglin is expressed in early erythroid precursors (EryP) and mesodermal precursors with hematogenic and endothelial potential. Aberrant expression of Endoglin affects mainly the erythroid lineage but also to a minor extent the myeloid and lymphoid lineages.
Adult Hematopoiesis. Endoglin expression is high in long term HSC in the KLS+ compartment and decreased in short-term HSC and MPP. In the KLS-compartment, Endoglin is transiently high expressed in MEP, pre-CFU-E and CFU-E., while dysregulation of Endoglin expression affects mainly the erythroid lineage.
Expression of Endoglin in Individual Hematopoietic Lineages. Endoglin might be involved in the differentiation of erythroid cells, but there are no functional roles assigned to Endoglin in mature cells of this lineage; Endothelial Endoglin was shown to mediate thrombocyte adhesion via the thrombocyte integrin complex αIIbβ3; The data imply that Endoglin is expressed and upregulated during macrophage differentiation and polarization. Endoglin most likely favors the pro-inflammatory M1 macrophage decision and Endoglin deficiency in macrophages renders an individual prone to infection; It was shown that Endoglin is highly expressed in MCs and localized to the secretory granules. TGF-β1 has an impact on several key functions in the different types of MCs of different origins and the TGF-β co-receptor Endoglin is expressed in MCs. Endoglin expression is present on mature immune cells of the innate, i.e., macrophages and MCs, and the adaptive, i.e., T-cells, immune system. Therefore, Endoglin might be a factor which helps to shape the immune response.
In conclusion, the presence of Endoglin in immune cells should help to increase/provide the treatments and knowledge toward processes leading to cancer and immune escape as well as pathologies depending on vascular dysfunction associated with inflammatory processes.
References
| Target | Cat. No. | Product Name | Expression System | Tag/Conjugate | Application | |
| ENG | DAG-P0303 | Human ENG peptide | N/A | Unconjugated | ELISA | Inquiry |
| Target | Cat. No. | Product Name | Size | Species Reactivity | Application | Detection Sample | |
| ENG | ABPR-0294 | Human ENG ELISA Matched Antibody Pair | ELISA | Inquiry | |||
| ABPR-0295 | Human ENG ELISA Matched Antibody Pair | ELISA | Inquiry | ||||
| DEIA1418 | CD105 Human ELISA Kit | 96T | Human | Quantitative | cell culture supernatant, urine, serum, plasma | Inquiry | |
| DEIA2944 | Mouse Endoglin/CD105 ELISA Kit | 96T | Mouse | Quantitative | cell culture supernatants, cell lysates, serum, plasma, urine | Inquiry | |
| DEIA-XYA991 | Endoglin ELISA Kit | 96T | Quantitative | cell lysates, serum, plasma | Inquiry | ||
| DEIA-BJ2067 | Rat ENG(Endoglin) ELISA Kit | 96T | Rat | Quantitative | Serum, plasma, tissue homogenates and other biological fluids. | Inquiry | |
| DEIA-BJ466 | Human sCD105/soluble Endoglin ELISA kit | 96T | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry |
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