Linked Life Data

11090062

Source:http://linkedlifedata.com/resource/pubmed/id/11090062

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-12-11
pubmed:abstractText
Signaling by vascular endothelial growth factors (VEGFs) through VEGF receptors (VEGFRs) plays important roles in vascular development and hematopoiesis. The authors analyzed the function of VEGF-C signaling through both VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis using a coculture of para-aortic splanchnopleural mesoderm (P-Sp) explants from mouse embryos with stromal cells (OP9). Vasculogenesis and angiogenesis were evaluated by the extent of vascular bed and network formation, respectively. Addition of VEGF-C to the P-Sp culture enhanced vascular bed formation and suppressed definitive hematopoiesis. Both vascular bed and network formations were completely suppressed by addition of soluble VEGFR-1-Fc competitor protein. Formation of vascular beds but not networks could be rescued by VEGF-C in the presence of the competitor, while both were rescued by VEGF-A. VEGFR-3-deficient embryos show the abnormal vasculature and severe anemia. Consistent with these in vivo findings, vascular bed formation in the P-Sp from the VEGFR-3-deficient embryos was enhanced to that in wild-type or heterozygous embryos, and hematopoiesis was severely suppressed. When VEGFR-3-Fc chimeric protein was added to trap endogenous VEGF-C in the P-Sp culture of the VEGFR-3-deficient embryos, vascular bed formation was suppressed and hematopoiesis was partially rescued. These results demonstrate that because VEGF-C signaling through VEGFR-2 works synergistically with VEGF-A, the binding of VEGF-C to VEGFR-3 consequently regulates VEGFR-2 signaling. In VEGFR-3-deficient embryos, an excess of VEGF-C signals through VEGFR-2 induced the disturbance of vasculogenesis and hematopoiesis during embryogenesis. This indicates that elaborated control through VEGFR-3 signaling is critical in vasculoangiogenesis and hematopoiesis. (Blood. 2000;96:3793-3800)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3793-800
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11090062-Animals, pubmed-meshheading:11090062-Blood Vessels, pubmed-meshheading:11090062-Cell Differentiation, pubmed-meshheading:11090062-Cell Line, pubmed-meshheading:11090062-Coculture Techniques, pubmed-meshheading:11090062-Embryo, Mammalian, pubmed-meshheading:11090062-Endothelial Growth Factors, pubmed-meshheading:11090062-Hematopoiesis, pubmed-meshheading:11090062-Humans, pubmed-meshheading:11090062-Immunohistochemistry, pubmed-meshheading:11090062-Mesoderm, pubmed-meshheading:11090062-Mice, pubmed-meshheading:11090062-Mice, Mutant Strains, pubmed-meshheading:11090062-Neovascularization, Physiologic, pubmed-meshheading:11090062-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:11090062-Receptors, Growth Factor, pubmed-meshheading:11090062-Receptors, Vascular Endothelial Growth Factor, pubmed-meshheading:11090062-Signal Transduction, pubmed-meshheading:11090062-Splanchnic Circulation, pubmed-meshheading:11090062-Stromal Cells, pubmed-meshheading:11090062-Vascular Endothelial Growth Factor C, pubmed-meshheading:11090062-Vascular Endothelial Growth Factor Receptor-3, pubmed-meshheading:11090062-Yolk Sac
pubmed:year
2000
pubmed:articleTitle
VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis.
pubmed:affiliation
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't