Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans

Abstract

Pregnancy-specific ␤1 glycoproteins (PSGs) are the most abundant fetal proteins in the maternal bloodstream in late pregnancy. They are secreted by the syncytiotrophoblast and are detected around day 14 postfertilization. There are 11 human PSG genes, which encode a family of proteins exhibiting significant conservation at the amino acid level. We and others have proposed that PSGs have an immune modulatory function. In addition, we recently postulated that they are proangiogenic due to their ability to induce the secretion of VEGF-A and the formation of tubes by endothelial cells. The cellular receptor(s) for human PSGs remain unknown. Therefore, we conducted these studies to identify the receptor for PSG1, the highest expressed member of the family. We show that removal of cell surface glycosaminoglycans (GAGs) by enzymatic or chemical treatment of cells or competition with heparin completely inhibited binding of PSG1. In addition, PSG1 did not bind to cells lacking heparan or chondroitin sulfate on their surface, and binding was restored upon transfection with all four syndecans and glypican-1. Importantly, the presence of GAGs on the surface of endothelial cells was required for the ability of PSG1 to induce tube formation. This finding indicates that the PSG1-GAG interaction mediates at least some of the PSG1 proposed functions.Pregnancy success requires that the maternal immune system does not attack the fetal trophoblast cells, which are in direct contact with maternal blood and express genes derived from both the mother and the father. In addition, during pregnancy major vascular adaptations are required to guarantee fetal growth and survival. These include uterine vessel dilation, remodeling of the maternal decidual arteries, and angiogenesis within the placenta villi, as reviewed in Ref.

Early Expression of Pregnancy-Specific Glycoprotein 22 (PSG22) by Trophoblast Cells Modulates Angiogenesis in Mice1

“…We have previously reported that human PSG1 binding to the HS chains of syndecans induces the formation of capillarylike structures by endothelial cells [35,36]. Because PSG22 also binds to syndecans, we hypothesized that this murine PSG might also induce endothelial tube formation.…”

Secretory/releasing proteome-based identification of plasma biomarkers in HBV-associated hepatocellular carcinoma

“…PSG9 belongs to the carcinoembryonic antigen family and is a highly glycosylated protein that is deregulated during colorectal carcinogenesis [28]. PSG1 regulates immunoreactions and has proangiogenic properties [29]. Furthermore, PSG9 interacts with AFP and is involved in the TGF-β signaling pathway, based on network analysis ( Figure S3).…”

The Placenta in Normal Pregnancy and Preeclampsia

“…79 CTB production of numerous isoforms of pregnancy-specific beta-1 glycoprotein (PSG-1) were also upregulated. Although their functions are not well understood, they appear to have vasculogenic 80,81 and immune properties. 82,83 Glypican 3, proposed as a receptor for some PSG family members, 84 was also upregulated.…”