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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-6-22
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pubmed:abstractText |
Inflammation and angiogenesis are associated with pathological disorders. TNF-alpha is a major inflammatory cytokine that also regulates angiogenesis. TNF-alpha has been shown to regulate Tie-2 and angiopoietin (Ang) expression, but the functional significance is less clear. In this study, we showed that TNF-alpha induced a weak angiogenic response in a mouse cornea assay. Systemic overexpression of Ang-1 or Ang-2 dramatically increased corneal angiogenesis induced by TNF-alpha. In the absence of TNF-alpha, neither Ang-1 nor Ang-2 promoted corneal angiogenesis. Low doses (0-25 ng/ml) of TNF-alpha increased vascular branch formation of cultured endothelial cells. Overexpression of Ang-1 or Ang-2 enhanced the effects of TNF-alpha. These data suggest that Tie-2 signaling synergistically amplifies and participates in TNF-alpha-mediated angiogenesis. In addition, high doses (>/=50 ng/ml) of TNF-alpha induced apoptosis in endothelial cells, but addition of Ang-1 or Ang-2 significantly reduced cell death. Enhanced endothelial cell survival was correlated with Akt phosphorylation. Collectively, our data reveal dual functional roles of Tie-2: low doses enhance TNF-alpha-induced angiogenesis, and high doses attenuate TNF-alpha-induced cell death. The study provides evidence supporting a role for Tie-2 in inflammatory angiogenesis.
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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 |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ANGPT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Angiopoietin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Angiopoietin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, TIE-2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0363-6135
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
287
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H187-95
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15210451-Angiopoietin-1,
pubmed-meshheading:15210451-Angiopoietin-2,
pubmed-meshheading:15210451-Animals,
pubmed-meshheading:15210451-Apoptosis,
pubmed-meshheading:15210451-Capillaries,
pubmed-meshheading:15210451-Cell Survival,
pubmed-meshheading:15210451-Cells, Cultured,
pubmed-meshheading:15210451-Endothelium, Vascular,
pubmed-meshheading:15210451-Humans,
pubmed-meshheading:15210451-Mice,
pubmed-meshheading:15210451-Mice, Inbred BALB C,
pubmed-meshheading:15210451-Neovascularization, Physiologic,
pubmed-meshheading:15210451-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15210451-Proto-Oncogene Proteins,
pubmed-meshheading:15210451-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15210451-Receptor, TIE-2,
pubmed-meshheading:15210451-Tumor Necrosis Factor-alpha
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pubmed:year |
2004
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pubmed:articleTitle |
Dual functional roles of Tie-2/angiopoietin in TNF-alpha-mediated angiogenesis.
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pubmed:affiliation |
Department of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Ave., Preston Research Bldg., Rm. 315, Nashville, TN 37232, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.
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