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: | College of Health & Life Sciences College of Health & Life Sciences > School of Biosciences College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine College of Health & Life Sciences > Aston Medical School |
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Additional Information: | Creative Commons Attribution Non-Commercial No Derivatives License |
Uncontrolled Keywords: | VEGF-C,,VEGFR-2/(KDR),placenta,endothelial cells,pregnancy,IUGR |
Publication ISSN: | 1699-5848 |
Last Modified: | 30 Sep 2024 10:13 |
Date Deposited: | 23 Dec 2014 15:40 |
Full Text Link: | |
Related URLs: |
http://www.hh.u ... 16_2/16_2_3.htm
(Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2001-04 |
Authors: |
Dunk, Caroline
Ahmed, Asif ( 0000-0002-8755-8546) |
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