Reactome | PSGs bind proteoglycans and TGF-beta1

PSGs bind proteoglycans and TGF-beta1

Stable Identifier

R-HSA-8870732

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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The pregnancy-specific glycoproteins (PSGs) are the most abundant trophoblastic proteins in maternal blood during human pregnancy. They are secreted by the syncytiotrophoblast and are detected around day 14 post fertilization. The PSG family belongs to the carcinoembryonic antigen family. There are ten human protein-coding PSG genes (PSG1- PSG9, PSG11) (Thompson et al. 1990). Several studies indicate that PSGs have immunoregulatory, proangiogenic, and anti-platelet functions. PSGs (PSG1) binds to cell surface proteoglycans that have covalently attached glycosaminoglycans (GAGs), specifically to syndecans 1-4 and glypican-1, to induce endothelial tube formation (Lisboa et al. 2011). PSG1 interacts with and activates Transforming growth factor beta 1 (TGFB1) (Blois et al. 2014, Moore & Dveksler 2014). During pregnancy, TGFB1 regulates many processes essential for pregnancy success including trophoblast invasion and proliferation, angiogenesis, extracellular matrix formation and tolerance to the foetal semi-allograft (Jones et al. 2006). TGFB1 also regulates the production of vascular endothelial growth factor (VEGF) and this may contribute to PSG1-induced VEGF-A secretion (Ha et al. 2010). Therefore the pro-angiogenic properties of some PSGs are mediated by two different mechanisms, TGF-beta mediated induction of VEGF-A, and direct interaction of PSGs with GAGs on the surface of endothelial cells.

Literature References

PubMed ID	Title	Journal	Year
23945545	Pregnancy-specific glycoprotein 1 (PSG1) activates TGF-? and prevents dextran sodium sulfate (DSS)-induced colitis in mice Freitag, N, Dveksler, GS, Fuss, I, Strober, W, Rifkin, D, Sulkowski, G, Tirado-González, I, Blois, SM, Klapp, BF, Warren, J	Mucosal Immunol	2014
21193412	Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through interaction with cell surface proteoglycans Aparicio, M, Warren, J, Sulkowski, G, Lisboa, FA, Zudaire, E, David, G, Dveksler, GS	J. Biol. Chem.	2011