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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 |
2011-2-4
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pubmed:abstractText |
Erythropoietin (EPO) enhances angiogenesis in the ischemic brain. Stroke induces secretion of tumor necrosis factor ? (TNF-?). We investigated the effect of TNF-? on EPO-induced in vitro angiogenesis in cerebral endothelial cells. Using a capillary-like tubular formation assay, we found that transient incubation of primary rat cerebral microvascular endothelial cells (RECs) with TNF-? substantially upregulated EPO receptor (EPOR) expression and addition of EPO into TNF-?-treated RECs significantly augmented the capillary-like tube formation. Blockage of TNF receptor 1 (TNFR1) suppressed TNF-?-upregulated EPOR expression and abolished EPO-induced tube formation. Attenuation of endogenous EPOR with small interfering RNA (siRNA) also inhibited EPO-enhanced tube formation. Treatment of RECs with EPO activated nuclear factor-kappa B (NF-?B) and Akt. Incubation of the TNF-?-treated endothelial cells with EPO activated vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), angiopoietin 1 (Ang1), and Tie2. Blockage of VEGFR2 and Tie2 resulted in reduction of EPO-augmented tube formation. These data indicate that interaction of TNF-? with TNFR1 sensitizes cerebral endothelial cells for EPO-induced angiogenesis by upregulation of EPOR, which amplifies the effect of EPO on activation of the VEGF/VEGFR2 and Ang1/Tie2 pathways. Our results provide the evidence for crosslink between TNF and EPOR to coordinate the onset of angiogenesis in cerebral endothelial cells.
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pubmed:grant |
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pubmed:commentsCorrections |
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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 Inducing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Angiopoietin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1559-7016
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pubmed:author |
pubmed-author:AluigiDanielle MarieDM,
pubmed-author:BolzMarianneM,
pubmed-author:ChoppMichaelM,
pubmed-author:ChrsitensenSørenS,
pubmed-author:FranciscoMoniche ÃlvarezMÃ,
pubmed-author:Moniche-AlvarezFranciscoF,
pubmed-author:SagerThomas NTN,
pubmed-author:SwanL CLC,
pubmed-author:SzaladAlexandraA,
pubmed-author:WangLeiL,
pubmed-author:WangXin LiXL,
pubmed-author:ZhangRui LanRL,
pubmed-author:ZhangZheng GangZG
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
640-7
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:20700128-Angiogenesis Inducing Agents,
pubmed-meshheading:20700128-Angiopoietin-1,
pubmed-meshheading:20700128-Animals,
pubmed-meshheading:20700128-Blotting, Western,
pubmed-meshheading:20700128-Capillaries,
pubmed-meshheading:20700128-Cell Proliferation,
pubmed-meshheading:20700128-Drug Synergism,
pubmed-meshheading:20700128-Endothelial Cells,
pubmed-meshheading:20700128-Erythropoietin,
pubmed-meshheading:20700128-Immunohistochemistry,
pubmed-meshheading:20700128-Male,
pubmed-meshheading:20700128-NF-kappa B,
pubmed-meshheading:20700128-Neovascularization, Physiologic,
pubmed-meshheading:20700128-Oncogene Protein v-akt,
pubmed-meshheading:20700128-Rats,
pubmed-meshheading:20700128-Rats, Wistar,
pubmed-meshheading:20700128-Receptors, Erythropoietin,
pubmed-meshheading:20700128-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:20700128-Receptors, Tumor Necrosis Factor, Type II,
pubmed-meshheading:20700128-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20700128-Transfection,
pubmed-meshheading:20700128-Tumor Necrosis Factor-alpha,
pubmed-meshheading:20700128-Vascular Endothelial Growth Factor A
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pubmed:year |
2011
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pubmed:articleTitle |
Tumor necrosis factor ? primes cerebral endothelial cells for erythropoietin-induced angiogenesis.
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pubmed:affiliation |
Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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