Abstract
The shedding mechanism for the tomoregulin (TR) ectodomain, which contains two follistatin modules and a single epidermal growth factor (EGF)-like domain, remains unclear. Our study provides the first evidence that proinflammatory cytokines, IL-1beta and TNF-alpha, induce TR-ectodomain shedding in cultured A172 human glioma cells, without affecting TR mRNA expression. In addition, it appears that this shedding process is induced via activation of the NF-kappaB signaling pathway; with consequent increase in the production of metalloproteinases. Furthermore, since due to erbB4 tyrosine phosphorylation TR may have functions similar to EGF/neuregulin (NRG) family growth factors, our results suggest that following inflammation-induced injury, increases in TR shedding may contribute to tissue growth and repair in the central nervous system.
MeSH terms
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3T3 Cells
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Animals
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Blotting, Western
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Dipeptides / pharmacology
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Glioma
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Humans
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Hydroxamic Acids / pharmacology
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Interleukin-1 / pharmacology*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Metalloendopeptidases / antagonists & inhibitors
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Mice
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NF-kappa B / metabolism
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Neoplasm Proteins*
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Dipeptides
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Hydroxamic Acids
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Interleukin-1
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Membrane Proteins
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N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide
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NF-kappa B
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Neoplasm Proteins
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RNA, Messenger
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TAPI-2
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TMEFF2 protein, human
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Tmeff1 protein, mouse
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Tumor Necrosis Factor-alpha
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Metalloendopeptidases