Abstract
The growth of blood and lymphatic vasculature is mediated in part by secreted polypeptides of the vascular endothelial growth factor (VEGF) family. The prototype VEGF binds VEGF receptor (VEGFR)-1 and VEGFR-2 and is angiogenic, whereas VEGF-C, which binds to VEGFR-2 and VEGFR-3, is either angiogenic or lymphangiogenic in different assays. We used an adenoviral gene transfer approach to compare the effects of these growth factors in adult mice. Recombinant adenoviruses encoding human VEGF-C or VEGF were injected subcutaneously into C57Bl6 mice or into the ears of nude mice. Immunohistochemical analysis showed that VEGF-C upregulated VEGFR-2 and VEGFR-3 expression and VEGF upregulated VEGFR-2 expression at 4 days after injection. After 2 weeks, histochemical and immunohistochemical analysis, including staining for the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the vascular endothelial marker platelet-endothelial cell adhesion molecule-1 (PECAM-1), and the proliferating cell nuclear antigen (PCNA) revealed that VEGF-C induced mainly lymphangiogenesis in contrast to VEGF, which induced only angiogenesis. These results have significant implications in the planning of gene therapy using these growth factors.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenoviridae / genetics
-
Animals
-
Cell Division
-
Cell Line
-
Endothelial Growth Factors / genetics
-
Endothelial Growth Factors / physiology*
-
Endothelium, Lymphatic / chemistry
-
Endothelium, Lymphatic / cytology
-
Endothelium, Lymphatic / physiology*
-
Endothelium, Vascular / chemistry
-
Endothelium, Vascular / cytology
-
Gene Expression
-
Genetic Vectors / genetics
-
Glycoproteins / analysis
-
Humans
-
Immunohistochemistry
-
Lymphokines / genetics
-
Lymphokines / physiology
-
Membrane Transport Proteins
-
Mice
-
Mice, Inbred C57BL
-
Mice, Nude
-
Neovascularization, Physiologic / physiology*
-
Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
-
Proliferating Cell Nuclear Antigen / analysis
-
Receptor Protein-Tyrosine Kinases / metabolism
-
Receptors, Growth Factor / metabolism
-
Receptors, Vascular Endothelial Growth Factor
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Skin / blood supply*
-
Skin / metabolism
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factor C
-
Vascular Endothelial Growth Factor Receptor-3
-
Vascular Endothelial Growth Factors
-
Vesicular Transport Proteins
-
beta-Galactosidase / genetics
-
beta-Galactosidase / metabolism
Substances
-
Endothelial Growth Factors
-
Glycoproteins
-
LYVE1 protein, human
-
Lymphokines
-
Membrane Transport Proteins
-
Platelet Endothelial Cell Adhesion Molecule-1
-
Proliferating Cell Nuclear Antigen
-
Receptors, Growth Factor
-
Recombinant Fusion Proteins
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factor C
-
Vascular Endothelial Growth Factors
-
Vesicular Transport Proteins
-
Xlkd1 protein, mouse
-
Receptor Protein-Tyrosine Kinases
-
Receptors, Vascular Endothelial Growth Factor
-
Vascular Endothelial Growth Factor Receptor-3
-
beta-Galactosidase