Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function.

Détails

ID Serval
serval:BIB_34E57645B5EF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function.
Périodique
FASEB Journal
Auteur⸱e⸱s
Veikkola T., Lohela M., Ikenberg K., Mäkinen T., Korff T., Saaristo A., Petrova T., Jeltsch M., Augustin H.G., Alitalo K.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Statut éditorial
Publié
Date de publication
2003
Volume
17
Numéro
14
Pages
2006-2013
Langue
anglais
Résumé
Vascular endothelial cells are characterized by a high degree of functional and phenotypic plasticity, which is controlled both by their pericellular microenvironment and their intracellular gene expression programs. To gain further insight into the mechanisms regulating the endothelial cell phenotype, we have compared the responses of lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs) to vascular endothelial growth factors (VEGFs). VEGFR-3-specific signals are sufficient for LEC but not BEC proliferation, as shown by the ability of the specific ligand VEGF-C156S to stimulate cell cycle entry only in LECs. On the other hand, we found that VEGFR-3 stimulation did not induce LEC cell shape changes typical of VEGFR-2-stimulated LECs, indicating receptor-specific differences in the cytoskeletal responses. Genes induced via VEGFR-2 also differed between BECs and LECs: angiopoietin-2 (Ang-2) was induced via VEGFR-2 in BECs and LECs, but the smooth muscle cell (SMC) chemoattractant BMP-2 was induced only in BECs. Both BECs and LECs were able to promote SMC chemotaxis, but contact with SMCs led to down-regulation of VEGFR-3 expression in BECs in a 3-dimensional coculture system. This was consistent with the finding that VEGFR-3 is down-regulated in vivo at sites of endothelial cell-pericyte/smooth muscle cell contacts. Collectively, these data show intrinsic cell-specific differences of BEC and LEC responses to VEGFs and identify a pericellular regulatory mechanism for VEGFR-3 down-regulation in endothelial cells.
Mots-clé
Angiopoietin-2/metabolism, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins/genetics, Bone Morphogenetic Proteins/metabolism, Cell Communication, Cell Division, Cell Movement, Cells, Cultured, Endothelium/cytology, Endothelium/drug effects, Endothelium, Vascular/cytology, Endothelium, Vascular/drug effects, Gene Expression Regulation, Humans, Lymphatic System/cytology, Muscle, Smooth/physiology, Phenotype, Transforming Growth Factor beta, Vascular Endothelial Growth Factor A/pharmacology, Vascular Endothelial Growth Factor Receptor-2/metabolism, Vascular Endothelial Growth Factor Receptor-3/metabolism
Pubmed
Web of science
Création de la notice
20/12/2012 17:03
Dernière modification de la notice
20/08/2019 13:21
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