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Cells. 2019 Oct 31;8(11). pii: E1369. doi: 10.3390/cells8111369.

Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions.

Author information

1
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA. sandra.blois@gmail.com.
2
Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5T 3H7, Canada. sandra.blois@gmail.com.
3
Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada. sandra.blois@gmail.com.
4
Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA. sandra.blois@gmail.com.
5
Department of Molecular Biology, Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain. sandra.blois@gmail.com.
6
Experimental and Clinical Research Center, a Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, and the Charité-Universitätsmedizin Berlin, AG GlycoImmunology, 13125 Berlin, Germany. sandra.blois@gmail.com.
7
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Medical Immunology, 13353 Berlin, Germany. sandra.blois@gmail.com.
8
Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892, USA. kyamada@dir.nidcr.nih.gov.
9
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, MD 20892, USA, and Detroit, MI 48201, USA. offererez@gmail.com.
10
Maternity Department "D," Division of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva 8410501, Israel. offererez@gmail.com.
11
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA. offererez@gmail.com.
12
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, MD 20892, USA, and Detroit, MI 48201, USA. ngomezlo@med.wayne.edu.
13
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA. ngomezlo@med.wayne.edu.
14
Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA. ngomezlo@med.wayne.edu.
15
Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5T 3H7, Canada. Lye@lunenfeld.ca.
16
Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada. boris.hinz@utoronto.ca.
17
Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, MI 48109, USA. prbchiefstaff@med.wayne.edu.
18
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, USA. prbchiefstaff@med.wayne.edu.
19
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA. prbchiefstaff@med.wayne.edu.
20
Detroit Medical Center, Detroit, MI 48201, USA. prbchiefstaff@med.wayne.edu.
21
Department of Obstetrics and Gynecology, Florida International University, Miami, FL 33199, USA. prbchiefstaff@med.wayne.edu.
22
Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, 1206 Geneva, Switzerland. gabriela.dveksler@usuhs.edu.
23
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA. gabriela.dveksler@usuhs.edu.

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 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 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 51 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:

adhesion; extravillous trophoblasts; integrin α5β1; migration; preeclampsia; pregnancy-specific glycoproteins

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