Abstract
Tumor necrosis factor-α (TNF-α) plays an important role in pathological angiogenesis associated with inflammatory response. Pim-3 kinase belonging to serine/threonine protein kinases is a potent suppressor of myc-induced apoptosis. We have recently demonstrated that Pim-3 plays an essential role in endothelial cell (EC) spreading and migration. In this study, we showed that TNF-α transiently increased Pim-3 mRNA expression, and this was mediated through Tumor necrosis factor-α receptor-1 (TNFR1) pathway in ECs. TNF-α could promote stabilization of Pim- 3 mRNA in ECs. Small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired TNF-α-induced formation of EC membrane protrusions in vitro. Furthermore, Pim-3 silencing inhibited EC sprouting in subcutaneous Matrigel in vivo. eNOS mRNA abundance was lower in Pim-3 siRNA transfected ECs compared with the control ECs. These observations suggest that Pim-3 plays a role in TNF-α-induced angiogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Movement
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Cells, Cultured
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Collagen / chemistry
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Collagen / metabolism
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Drug Combinations
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Female
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Gene Expression
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Gene Silencing / drug effects
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Human Umbilical Vein Endothelial Cells / cytology
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Human Umbilical Vein Endothelial Cells / metabolism*
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Humans
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Laminin / chemistry
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Laminin / metabolism
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Neoplasms / blood supply*
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Neoplasms / pathology
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism*
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Nitric Oxide Synthase Type III / genetics
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Nitric Oxide Synthase Type III / metabolism*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proteoglycans / chemistry
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Proteoglycans / metabolism
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA Stability
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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RNA, Small Interfering / pharmacology
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Receptors, Tumor Necrosis Factor, Type I / genetics
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Receptors, Tumor Necrosis Factor, Type I / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism*
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Up-Regulation
Substances
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Drug Combinations
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Laminin
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Proteoglycans
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Proto-Oncogene Proteins
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RNA, Messenger
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RNA, Small Interfering
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Receptors, Tumor Necrosis Factor, Type I
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Tumor Necrosis Factor-alpha
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matrigel
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Collagen
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NOS3 protein, human
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Nitric Oxide Synthase Type III
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PIM3 protein, human
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Protein Serine-Threonine Kinases