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

Dunk, Caroline and Ahmed, Asif (2001). Expression of VEGF-C and activation of its receptors VEGFR-2 and VEGFR-3 in trophoblast. Histology and Histopathology, 16 (2), pp. 359-375.

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 gestationally-matched 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 dose-dependant phosphorylation of VEGFR-2 in trophoblast cells as well as stimulating DNA synthesis. In addition, premixing VEGF165 with heparin sulphate proteoglycan potentiated trophoblast proliferation and the association of phospho-ERK with the VEGFR-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 abnormal villous development observed in IUGR placenta.

Divisions: Life & Health Sciences
Life & Health Sciences > Biosciences
Aston Medical School
Uncontrolled Keywords: VEGF-C,,VEGFR-2/(KDR),placenta,endothelial cells,pregnancy,IUGR
Full Text Link: http://www.hh.um.es/Abstracts/Vol_16/16_2/16_2_3.htm
Related URLs:
Published Date: 2001-04
Authors: Dunk, Caroline
Ahmed, Asif

Export / Share Citation


Statistics

Additional statistics for this record