Uniformed Services University of the Health Sciences
Department of Pathology
4301 Jones Bridge Road, C1094
Bethesda, Maryland 20814-4799
Phone: (301) 295-3450
fax: (301) 295-1640
Our laboratory studies the functions of members of the carcinoembryonic antigen (CEA) gene family, known as pregnancy specific glycoproteins (PSGs). PSGs are expressed by the placenta of rodents and humans, which share the same type of placentation, known as hemochorial. PSGs are secreted into the maternal circulation in increasing amounts, until term. Low PSG concentrations in serum correlate with several pregnancy pathologies suggesting that they are important for successful pregnancy. We are using molecular, cell biology and immunology techniques to understand the function of the 17 murine and of the 11 human pregnancy specific glycoprotein family members. We have generated several human and murine recombinant PSGs for our studies. We have found that PSGs regulate the secretion of cytokines in vivo and in vitro. Most importantly, we have shown that human PSG1 activates the anti-inflammatory cytokine transforming growth factor beta, making PSG1one of the few known activators of this important cytokine. In addition, we have characterized the receptor for several PSGs and found that they induce endothelial tube formation and induce the secretion of vascular endothelial growth factor, an important modulator of angiogenesis. Therefore, our studies indicate that PSGs are involved in two processes, which are essential for pregnancy success: the establishment of the fetal-maternal blood supply and the regulation of the immune responses to the semi-allogeneic fetus.
R. Waterhouse, C. Ti and G. S. Dveksler. Murine CD9 is the Receptor for Pregnancy Specific Glycoprotein 17. J. Exp. Med. 195:277-82 (2002).
D. Ellermann, C. Ha, D. Myles, P. Primakoff and G. Dveksler. Direct Binding of the Ligand PSG17 to CD9 at a site active in sperm-egg fusion. Mol. Biol. Cell.14: 5098-103 (2003).
A. McLellan, B. Fischer, H. Hameister, G. Dveksler, T. Hori, F. Wynne, M. Ball, K. Okumura, T. Moore and W. Zimmermann. Structure and evolution of the mouse pregnancy-specific glycoprotein gene locus. BMC Genomics 6 (1):4 (2005).
J Wu, B. Johnson, Y. Chen, C. Ha and G. Dveksler. Murine pregnancy-specific glycoprotein 23 induces the proangiogenic factors transforming -growth factor beta 1 and vascular endothelial growth factor A in cell types involved in vascular remodeling in pregnancy. Biol.of Reprod., 79:1054-61 (2008)
Ha, CT, Wu JA, Irmak S, Lisboa FA, Dizon AM, Warren JW, Ergun S, Dveksler GS. Human pregnancy specific beta-1-glycoprotein (PSG1) has a potential role in placental vascular morphogenesis. Biol. of Reprod., 83: 27-35 (2010).
Lisboa FA, Warren J, Sulkowski G, Aparicio M, David G, Zudaire E, Dveksler GS. Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through interaction with cell surface proteoglycans. J. Biol. Chem. 286:7577-86 (2011).
Sulkowski GN, Warren J, Ha CT, Dveksler GS. Characterization of receptors for murine pregnancy specific glycoproteins 17 and 23. Placenta 32:603-610 (2011).
Blois SM, Tirado-Gonzalez I, Wu J, Barrientos, G, Johnson B, Warren J, Freitag N, Klapp BF, Irmak, S, Ergun, S, Dveksler, GS. Early expression of Pregnancy-specific glycoprotein 22 (PSG22) by trophoblast cells modulates angiogenesis in mice. Biol. of Reprod.86:191 (2012).