Publication:
Expression of VEGF-C and activation of its receptors VEGFR-2 and VEGFR-3 in trophoblast

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Authors
Dunk, C. ; Ahmed, A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Placental villous development requires the co-ordinated action of angiogenic factors on both endothelial and trophoblast cells. Like vascular endothelial growth factor (VEGF), VEGF-C increases vascular permeability, stimulates endothelial cell proliferation and migration. In the present study, we investigated the expression of VEGF-C and its receptors VEGFR-3 and VEGFR-2 in normal and intrauterine growth-restricted (IUGR) placenta. Immunolocalisation studies showed that like VEGF and VEGFR-1, VEGF-C, VEGFR-3 and VEGFR-2 co-localised to the syncytiotrophoblast, to cells in the maternal decidua, as well as to the endothelium of the large placental blood vessels. Western blot analysis demonstrated a significant decrease in placental VEGF-C and VEGFR-3 protein expression in severe IUGR as compared to gestationallymatched third trimester pregnancies. Conditioned medium from VEGF-C producing pancreatic carcinoma (Suit-2) and endometrial epithelial (Hec-1B) cell lines caused an increased association of the phosphorylated extracellular signal regulated kinase (ERK) in VEGFR-3 immunoprecipitates from spontaneously transformed first trimester trophoblast cells. VEGF121 caused dosedependant phosphorylation of VEGFR-2 in trophoblast cells as well as stimulating DNA svnthesis. In addition. premixing VEGFl with Yheparin sÚlphate proteoglycan wtentiated trooho8ast oroliferation and the association Lf p h ~ s p hw~ith- t i~e V~E~GF R-2 receptor. VEGF165- mediated DNA synthesis was inhibited by anti-VEGFR- 2 neutralising antibody. The results demonstrate functional VEGFR-2 and VEGFR-3 receptors on trophoblast and suggest that the decreased expression of VEGF-C and VEGFR-3 may contribute to the abnormai villous development observed in IUGR placenta.
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Citation
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