Novel vascular roles of human endoglin in pathophysiology

HDAC6 Enhances Endoglin Expression through Deacetylation of Transcription Factor SP1, Potentiating BMP9-Induced Angiogenesis

“…It predominantly binds to the ligands BMP9 and BMP10 [ 51 , 52 ]. ENG is known to play a crucial role in maintaining vascular integrity [ 50 , 53 ]. Homozygous mutations in mice result in embryonic lethality, and certain point mutations in human ENG are linked to hereditary hemorrhagic telangiectasia (HHT) [ 50 ].…”

Editorial: Role of membrane-bound and circulating endoglin in disease

“…Approximately 90% of the protein is located within its extracellular region, which upon being targeted, at least by metalloproteases (MMP) MMP-14 and MMP-12, can be shed as a circulating form of endoglin also named as soluble endoglin (sEng) ( 5 , 6 ). Thus, it is not surprising that the extracellular region has attracted many structural and functional studies ( 1 – 3 ). The extracellular region of endoglin encompasses two distinct domains: (i) a juxtamembrane Zona Pellucida (ZP) domain expanding ~260 amino acids at the C-terminus, with eight conserved cysteine residues and divided into two well-defined subdomains (ZP-C and ZP-N); and (ii) an orphan domain (OD) at the N-terminus, named so due to its lack of significant homology with other protein families ( 7 , 8 ).…”

“…Thus, the OD is involved in the recognition and signaling of members from the transforming growth factor-β (TGF-β) family, like bone morphogenetic protein (BMP)-9 and BMP-10 ( 8 , 9 ). On the other hand, the ZP domain is involved in cell adhesion through its interaction with integrins of the arginine-glycine-aspartic acid (RGD) subfamily, like α5β1 and αIIbβ3, which recognize the RGD motif located within the ZP-N subdomain of endoglin ( 3 ). In addition, the short (14 residues) cytoplasmic domain of endoglin is constitutively phosphorylated in serine and threonine residues and is involved in the organization of the actin cytoskeleton and TGF-β/BMP signaling ( 10 – 12 ).…”

“…Since its discovery and characterization in the early 1990s, a growing body of evidence supports the involvement of endoglin in a broad range of patho-physiological conditions, including physiological and pathological angiogenesis, vascular pathology, preeclampsia, tumor vascularization, hemostasis or tumor malignancy ( 1 – 3 ). This Research Topic draws together a series of reports focusing on different and novel aspects of endoglin on etiology, diagnostics, prognosis, or predictive purposes in several conditions such as hereditary hemorrhagic telangiectasia, endothelial dysfunction, cancer, hyperglycemia, hypercholesterolemia, septic syndrome, and systemic sclerosis.…”

Unveiling Endoglin non canonical regulation: spotlight on the new role of the uPAR pathway

“…In that context, the ENG gene coding for Endoglin is, together with ACVRL1 and SMAD4 genes, one of the 3 major genes for Hereditary Hemorrhagic Telangiectasia (HHT), a multiorgan rare vascular disease 6 . More recent works have highlighted new functions for Endoglin 7 , in particular in leukocyte adhesion and transmigration under inflammatory conditions 8 , but also in platelets biology 9 and cancer-associated fibroblasts 10 . There is then accumulating evidence that Endoglin and its soluble form (S-Endoglin) are involved in many human diseases 11 such as thrombosis 9 , coronary atherosclerosis 12 , preeclampsia 13 , hypertension 14 , autoimmune disease 15 , some cancers 16 , and beyond.…”