Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signaling

link: https://pubmed.ncbi.nlm.nih.gov/28530660/

Jin, Y., Muhl, L., Burmakin, M., Wang, Y., Duchez, A. C., Betsholtz, C., Arthur, H. M., & Jakobsson, L. (2017). Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling. Nature cell biology, 19(6), 639–652. https://doi.org/10.1038/ncb3534

Typically, loss-of-function indicates that less of a protein is produced or that some of its functions have been compromised.
Loss-of-function mutations are typically recessive because a single “good” copy of the gene is sufficient. Endoglin is predominantly expressed on activated endothelial cells. In addition, it is found on the surface of several other cell types, including hematopoietic progenitor cells, bone marrow stromal fibroblasts, activated monocytes, differentiated macrophages, melanocytes, and syncytiotrophoblasts of placenta. Endoglin is important because it is an accessory receptor for the cytokine transforming growth factor- (TGF-), which regulates the proliferation, migration, adhesion, and apoptosis of numerous cell types.

According to Jin Y., et al. (2017), Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin (ENG) cause hereditary haemorrhagic telangiectasia-1, which is characterized by vascular malformations promoted by vascular endothelial growth factor A. (VEGFA). Hereditary hemorrhagic telangiectasia is an inherited disorder characterized by the development of arteriovenous malformations (AVMs) between the arteries and veins. The most commonly affected organs are the nose, lungs, brain, and liver.

These AVMs may enlarge over time and bleed or rupture, sometimes resulting in catastrophic complications.

The most prevalent symptom is spontaneous and unprovoked nosebleeds, which may occur daily. Persistent bleeding from the nose and gastrointestinal tract can result in severe iron deficiency anemia and diminished quality of life.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a genetic disorder inherited from your parents. Even within the same family, its severity can vary greatly from person to person.

cross-references:
Kopczyńska, E., & Makarewicz, R. (2012). Endoglin – a marker of vascular endothelial cell proliferation in cancer. Contemporary oncology (Poznan, Poland), 16(1), 68–71. https://doi.org/10.5114/wo.2012.27340

Dallas NA, Samuel S, Xia L, Fan F, Gray MJ, Lim SJ, Ellis LM. Endoglin (CD105): A marker of tumor vasculature and potential target for therapy. Clin Cancer Res. 2008;14:1931–7.

Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP. Defective angiogenesis in mice lacking endoglin. Science. 1999; 284: 1534–1537.

Barbara NP, Wrana JL, Letarte M. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-β superfamily. J Biol Chem. 1999; 274: 584–594.

https://www.mayoclinic.org/diseases-conditions/hht/symptoms-causes/syc-20351135#:~:text=Hereditary%20hemorrhagic%20telangiectasia%20(tuh%2Dlan,%2C%20lungs%2C%20brain%20and%20liver.