Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions
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Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions. / Rattila, Shemona; Dunk, Caroline E E; Im, Michelle; Grichenko, Olga; Zhou, Yan; Yanez-Mo, Maria; Blois, Sandra M; Yamada, Kenneth M; Erez, Offer; Gomez-Lopez, Nardhy; Lye, Stephen J; Hinz, Boris; Romero, Roberto; Cohen, Marie; Dveksler, Gabriela.
In: CELLS-BASEL, Vol. 8, No. 11, 31.10.2019.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions
AU - Rattila, Shemona
AU - Dunk, Caroline E E
AU - Im, Michelle
AU - Grichenko, Olga
AU - Zhou, Yan
AU - Yanez-Mo, Maria
AU - Blois, Sandra M
AU - Yamada, Kenneth M
AU - Erez, Offer
AU - Gomez-Lopez, Nardhy
AU - Lye, Stephen J
AU - Hinz, Boris
AU - Romero, Roberto
AU - Cohen, Marie
AU - Dveksler, Gabriela
PY - 2019/10/31
Y1 - 2019/10/31
N2 - 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 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 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 51 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.
AB - 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 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 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 51 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.
KW - Cell Adhesion
KW - Cell Line
KW - Cell Membrane/metabolism
KW - Cell Movement
KW - Extracellular Matrix/metabolism
KW - Female
KW - Focal Adhesion Protein-Tyrosine Kinases/metabolism
KW - Heparitin Sulfate/metabolism
KW - Humans
KW - Immobilized Proteins/chemistry
KW - Integrin alpha5beta1/metabolism
KW - Placenta/metabolism
KW - Pre-Eclampsia/diagnosis
KW - Pregnancy
KW - Pregnancy Trimester, First
KW - Pregnancy-Specific beta 1-Glycoproteins/analysis
KW - Protein Binding
KW - Trophoblasts/cytology
U2 - 10.3390/cells8111369
DO - 10.3390/cells8111369
M3 - SCORING: Journal article
C2 - 31683744
VL - 8
JO - CELLS-BASEL
JF - CELLS-BASEL
SN - 2073-4409
IS - 11
ER -