Gregory A L, Xu G, Sotov V, Letarte M
Molecular Structure and Function Program, Hospital for Sick Children, Department of Immunology, Canada; Heart & Stroke Richard Lewar Centre of Excellence, University of Toronto, Canada.
Placenta. 2014 Feb;35 Suppl:S93-9. doi: 10.1016/j.placenta.2013.10.020. Epub 2013 Nov 8.
The cellular expression, structure and function of endoglin, and its implication in several vascular disorders remain enigmatic, even 30 years after its discovery. Endoglin (CD105) is a homodimeric glycoprotein (180 kDa) constitutively expressed in the vascular endothelium. It is essential for cardiovascular development and mutations in the ENG gene lead to Hereditary Hemorrhagic Telangiectasia, a disorder characterized by arteriovenous malformations. Endoglin is also expressed in the syncytiotrophoblast throughout pregnancy, but transiently upregulated in the extravillous trophoblast of anchoring villi. Endoglin modulates responses to several TGF-β superfamily ligands and is essential for the negative regulation by TGF-β isoforms 1 and 3 of extravillous trophoblast differentiation. Membrane endoglin binds endothelial NO synthase and regulates its activation and vasomotor tone. There is also a circulating soluble form of endoglin (sEng; 65 kDa); its levels in the serum of women with preeclampsia are increased and correlated with disease severity. The exact sequence of sEng is still unresolved and the proposed mechanism of release from the syncytium by metalloproteases would not yield the expected size protein. The nature of the ligand sequestered by sEng is also an enigma. sEng is said to block the effects of TGF-β on NO-mediated vasorelaxation. However, sEng alone cannot scavenge these ligands for which it has very low affinity. sEng binds with high affinity to BMP9, which stimulates secretion from endothelial cells of the vascoconstrictor endothelin-1, also implicated in endothelial cell stabilization. It remains to be determined if scavenging of circulating BMP9 by sEng is important in preeclampsia and regulation of hypertension.
内皮糖蛋白的细胞表达、结构和功能，及其在多种血管疾病中的意义仍然不明，即便在其被发现30年后仍是如此。内皮糖蛋白（CD105）是一种同型二聚体糖蛋白（180 kDa），在血管内皮中组成性表达。它对心血管发育至关重要，ENG基因的突变会导致遗传性出血性毛细血管扩张症，这是一种以动静脉畸形为特征的疾病。内皮糖蛋白在整个孕期的合体滋养层中也有表达，但在固定绒毛的绒毛外滋养层中会短暂上调。内皮糖蛋白调节对几种转化生长因子-β超家族配体的反应，并且对于转化生长因子-β同工型1和3对绒毛外滋养层分化的负调节至关重要。膜内皮糖蛋白与内皮型一氧化氮合酶结合并调节其激活和血管舒缩张力。也有一种循环的可溶性内皮糖蛋白形式（sEng；65 kDa）；子痫前期女性血清中的sEng水平升高，且与疾病严重程度相关。sEng的确切序列仍未确定，关于其通过金属蛋白酶从合体中释放的推测机制无法产生预期大小的蛋白质。被sEng螯合的配体的性质也是一个谜。据说sEng会阻断转化生长因子-β对一氧化氮介导的血管舒张的作用。然而，单独的sEng无法清除这些它亲和力很低的配体。sEng与骨形态发生蛋白9（BMP9）高亲和力结合，BMP9会刺激血管收缩剂内皮素-1从内皮细胞分泌，内皮素-1也与内皮细胞稳定有关。sEng清除循环中的BMP9在子痫前期和高血压调节中是否重要仍有待确定。
