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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-2-21
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pubmed:abstractText |
Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo(p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction (p < 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis (annexin V staining, p < 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n = 3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:issn |
1423-0135
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pubmed:author |
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pubmed:copyrightInfo |
Copyright (c) 2007 S. Karger AG, Basel.
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pubmed:issnType |
Electronic
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pubmed:volume |
45
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
153-63
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17962719-Angiogenesis Inhibitors,
pubmed-meshheading:17962719-Animals,
pubmed-meshheading:17962719-Apoptosis,
pubmed-meshheading:17962719-Cell Proliferation,
pubmed-meshheading:17962719-Cell Survival,
pubmed-meshheading:17962719-Cells, Cultured,
pubmed-meshheading:17962719-Chick Embryo,
pubmed-meshheading:17962719-Chorioallantoic Membrane,
pubmed-meshheading:17962719-Endothelial Cells,
pubmed-meshheading:17962719-Fibroblast Growth Factor 2,
pubmed-meshheading:17962719-Humans,
pubmed-meshheading:17962719-Mice,
pubmed-meshheading:17962719-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17962719-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17962719-Neovascularization, Physiologic,
pubmed-meshheading:17962719-Oligonucleotides, Antisense,
pubmed-meshheading:17962719-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17962719-Phosphorylation,
pubmed-meshheading:17962719-Protein Kinase Inhibitors,
pubmed-meshheading:17962719-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:17962719-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17962719-Signal Transduction,
pubmed-meshheading:17962719-Time Factors,
pubmed-meshheading:17962719-Tissue Culture Techniques,
pubmed-meshheading:17962719-Transfection
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pubmed:year |
2008
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pubmed:articleTitle |
Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo.
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pubmed:affiliation |
Institute of Physiology, Medical Policlinic, Ludwig Maximilians University, Munich, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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