CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
Pro-angiogenic effects of pregnancy-specific glycoproteins in endothelial and extravillous trophoblast cells
Autor/es:
FLORIAN KLEEFELDT; MARIA L RIBEIRO; SHEMONA RATTILA; JIMENA S BELTRAME; GABRIELA DVEKSLER; ANGELA BALLESTEROS; SÜLEYMAN ERGÜN
Revista:
REPRODUCTION
Editorial:
BIOSCIENTIFICA LTD
Referencias:
Lugar: Bristol; Año: 2020 vol. 160 p. 737 - 750
ISSN:
1470-1626
Resumen:
We previously reported that binding to heparan sulfate (HS) is required for the ability of the placentally secreted pregnancy-specificglycoprotein 1 (PSG1) to induce endothelial tubulogenesis. PSG1 is composed of four immunoglobulin-like domains but whichdomains of the protein bind to HS remains unknown. To analyze the interaction of PSG1 with HS, we generated several recombinantproteins, including the individual domains, chimeric proteins between two PSG1 domains, and mutants. Using flow cytometric andsurface plasmon resonance studies, we determined that the B2 domain of PSG1 binds to HS and that the positively charged aminoacids encompassed between amino acids 43?59 are required for this interaction. Furthermore, we showed that the B2 domain ofPSG1 is required for the increase in the formation of tubes by endothelial cells (EC) including a human endometrial EC line and twoextravillous trophoblast (EVT) cell lines and for the pro-angiogenic activity of PSG1 observed in an aortic ring assay. PSG1 enhancedthe migration of ECs while it increased the expression of matrix metalloproteinase-2 in EVTs, indicating that the pro-angiogenic effectof PSG1 on these two cell types may be mediated by different mechanisms. Despite differences in amino acid sequence, we observedthat all human PSGs bound to HS proteoglycans and confirmed that at least two other members of the family, PSG6 and PSG9,induce tube formation. These findings contribute to a better understanding of the pro-angiogenic activity of human PSGs and stronglysuggest conservation of this function among all PSG family members.