VEGF is required for growth and survival in neonatal mice.

Details

Serval ID
serval:BIB_1FA4D9BA95D7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
VEGF is required for growth and survival in neonatal mice.
Journal
Development
Author(s)
Gerber H.P., Hillan K.J., Ryan A.M., Kowalski J., Keller G.A., Rangell L., Wright B.D., Radtke F., Aguet M., Ferrara N.
ISSN
0950-1991 (Print)
ISSN-L
0950-1991
Publication state
Published
Issued date
1999
Volume
126
Number
6
Pages
1149-1159
Language
english
Abstract
We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.
Keywords
Age Factors, Animals, Animals, Newborn/growth &amp, development, Apoptosis, Body Constitution/physiology, Capillaries/cytology, Cell Division, Endothelial Growth Factors/genetics, Endothelium, Vascular/drug effects, Gene Targeting, Genes, Essential, Heart Defects, Congenital, Immunoglobulin G/genetics, Immunoglobulin G/pharmacology, Interferon-alpha/pharmacology, Kidney/abnormalities, Kidney/blood supply, Liver/abnormalities, Liver/blood supply, Lymphokines/genetics, Mice, Mice, Mutant Strains, Mutagenesis, Neovascularization, Physiologic, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins/pharmacology, Receptor Protein-Tyrosine Kinases/genetics, Receptor Protein-Tyrosine Kinases/pharmacology, Receptors, Growth Factor/genetics, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins/pharmacology, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factors
Pubmed
Web of science
Create date
28/01/2008 11:39
Last modification date
20/08/2019 12:55
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