Role of Membrane-Bound and Circulating Endoglin in Disease

Endoglin (Eng), alias CD105, is a transmembrane glycoprotein whose mutations are responsible for a rare pathology called hereditary hemorragic telangectasia type 1. In addition, Eng seems to be implicated in a huge variety of pathologies including cancer, hypertension, atherosclerosis and metabolic diseases. Eng acts as an auxiliary receptor for several the TGF-beta family members, including BMP9 and BMP10. Recently, Eng was demonstrated to have a role beyond the TGF-beta pathway by acting as an adhesion molecule, implicated in vessel stabilization and platelets adhesion to endothelium. Upon cleavage of membrane-bound Eng, a soluble form (sEng) can be released, whose increased levels in circulation are regarded as a biomarker of preeclampsia. sEng is also a biomarker of metabolic syndrome-related symptoms and pathologies such as hypercholesterolemia, hyperglycemia, arterial hypertension, diabetes mellitus, and liver and kidney disease. Furthermore, sEng has also been reported to be of prognostic value in prostate, breast and gastrointestinal cancers.

Both Eng and sEng are involved in a wide variety of pathologies. However, their underlying molecular mechanisms are poorly understood. Eng is predominantly expressed in endothelial cells, playing a key role in vascular homeostasis, and its dysregulated expression is associated with different vascular-related disorders. In addition, sEng was initially described as a biomarker in preeclampsia, among other pathologies, but later studies also support a pathogenic role. Thus, sEng appears to participate in the development of endothelial dysfunction contributing to the development of arterial hypertension or pulmonary arterial hypertension, suggesting that high levels of sEng promote metabolic syndrome symptoms and complications. However, its cut-off concentration to be considered pathologic has not been completely elucidated. The involvement of Eng and sEng in new diseases remains to be explored. Interestingly, endothelial dysfunction participates in Covid-19 pathogenesis, but no information concerning Eng or sEng in Covid-19 patients is currently available. Overall, the main goal of this Research Topic is to better understand the molecular role of Eng and sEng in Pathology.

The aim of this research topic is to bring together the most recent findings on membrane-bound endoglin (Eng) and its circulating form of soluble endoglin (sEng).

Among others, authors could focus on:
• The involvement of membrane Eng in vascular pathology and vessels development/stabilization.
• The sEng biomarker to better characterize its function and its critical cut-off concentration as a disease marker.
• The role of Eng and/or sEng in cardiovascular, metabolic, liver, and kidney diseases, rare diseases, cancer and covid/SARS syndromes.
• The function of Eng and/or sEng, under the pathological setting, in endothelial, epithelial, mesenchymal stem, fibroblast, and smooth muscle cells, as well as in hematopoietic cells of the innate- and adaptive immune system.

This Research Topic’s aim is to improve the knowledge of this intriguing and not completely understood molecule.

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