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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2009-11-6
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pubmed:abstractText |
Slits are large, secreted repulsive axon guidance molecules. Recent genetic studies revealed that the Slit3 is dispensable for neural development but required for non-neuron-related developmental processes, such as the genesis of the diaphragm and kidney. Here we report that Slit3 potently promotes angiogenesis, a process essential for proper organogenesis during embryonic development. We observed that Slit3 is expressed and secreted by both endothelial cells and vascular smooth muscle cells in vasculature and that the Slit cognate receptors Robo1 and Robo4 are universally expressed by endothelial cells, suggesting that Slit3 may act in paracrine and autocrine manners to regulate endothelial cells. Cellular function studies revealed that Slit3 stimulates endothelial-cell proliferation, promotes endothelial-cell motility and chemotaxis via interaction with Robo4, and accelerates endothelial-cell vascular network formation in vitro with a specific activity comparable with vascular endothelial growth factor. Furthermore, Slit3 stimulates neovessel sprouting ex vivo and new blood vessel growth in vivo. Consistent with these observations, the Slit3 knockout mice display disrupted angiogenesis during embryogenesis. Taken together, our studies reveal that the repulsive axon guidance molecule Slit3 is a novel and potent angiogenic factor and functions to promote angiogenesis in coordinating organogenesis during embryonic development.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ROBO4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SLIT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Slit3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/rho GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/roundabout protein
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
5
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pubmed:volume |
114
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4300-9
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pubmed:dateRevised |
2010-11-8
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pubmed:meshHeading |
pubmed-meshheading:19741192-Angiogenic Proteins,
pubmed-meshheading:19741192-Animals,
pubmed-meshheading:19741192-Axons,
pubmed-meshheading:19741192-Cell Line,
pubmed-meshheading:19741192-Chick Embryo,
pubmed-meshheading:19741192-Endothelial Cells,
pubmed-meshheading:19741192-Gene Expression Regulation, Developmental,
pubmed-meshheading:19741192-Humans,
pubmed-meshheading:19741192-Male,
pubmed-meshheading:19741192-Membrane Proteins,
pubmed-meshheading:19741192-Mice,
pubmed-meshheading:19741192-Mice, Inbred C57BL,
pubmed-meshheading:19741192-Mice, Knockout,
pubmed-meshheading:19741192-Neovascularization, Physiologic,
pubmed-meshheading:19741192-Nerve Tissue Proteins,
pubmed-meshheading:19741192-Neurogenesis,
pubmed-meshheading:19741192-Rats,
pubmed-meshheading:19741192-Rats, Inbred F344,
pubmed-meshheading:19741192-Receptors, Cell Surface,
pubmed-meshheading:19741192-Receptors, Immunologic,
pubmed-meshheading:19741192-Recombinant Proteins,
pubmed-meshheading:19741192-Signal Transduction,
pubmed-meshheading:19741192-Vascular Endothelial Growth Factor A,
pubmed-meshheading:19741192-Vascular Endothelial Growth Factor Receptor-2,
pubmed-meshheading:19741192-rho GTP-Binding Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
Repulsive axon guidance molecule Slit3 is a novel angiogenic factor.
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pubmed:affiliation |
Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602-4712, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, N.I.H., Extramural
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