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Interaction of pregnancy-specific glycoprotein 1 with integrin Α5β1 is a modulator of extravillous trophoblast functions

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Item Type:Article
Title:Interaction of pregnancy-specific glycoprotein 1 with integrin Α5β1 is a modulator of extravillous trophoblast functions
Creators Name:Rattila, S. and Dunk, C.E.E. and Im, M. and Grichenko, O. and Zhou, Y. and Cohen, M. and Yanez-Mo, M. and Blois, S.M. and Yamada, K.M. and Erez, O. and Gomez-Lopez, N. and Lye, S.J. and Hinz, B. and Romero, R. and Dveksler, G.
Abstract:Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin α5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to α5β1 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to α5β1 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy.
Keywords:Pregnancy-Specific Glycoproteins, Extravillous Trophoblasts, Integrin α5ß1, Adhesion, Migration, Preeclampsia
Page Range:1369
Date:31 October 2019
Official Publication:https://doi.org/10.3390/cells8111369
PubMed:View item in PubMed

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