Abstract
Cardiotrophin-like cytokine (CLC), also known as novel neurotrophin-1/B cell stimulating factor-3 (NNT-1/BSF-3), is a recently identified member of the interleukin (IL)-6 family of cytokines that share gp130 as a signal-transducing receptor component. In this study, we demonstrate that CLC is expressed in fetal mouse neuroepithelial cells and has a potential to induce their astrocyte differentiation in a synergistic manner with bone-morphogenetic protein (BMP)-2, which is also expressed in the fetal mouse brain. CLC-stimulation led to promoter activation of the gene for an astrocyte marker, glial fibrillary acidic protein (GFAP), which was clearly inhibited by expression of a dominant negative form of a transcription factor, STAT3, or by introduction of a mutation in a single STAT3-binding site in the promoter, suggesting a critical role of STAT3 in the CLC-induced GFAP transcription. These results suggest that CLC plays a role in astrocyte differentiation via STAT3 activation within the developing brain.
Copyright 2002 Elsevier Science Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology*
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Astrocytes / metabolism
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Binding Sites
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / metabolism
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Brain / metabolism
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Cell Differentiation
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Cells, Cultured
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Cytokines / metabolism
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Cytokines / physiology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Genes, Dominant
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Glial Fibrillary Acidic Protein / metabolism
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Immunoblotting
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Mice
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Mice, Inbred ICR
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Microscopy, Fluorescence
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Neurons / metabolism*
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Phosphorylation
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Promoter Regions, Genetic
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Protein Binding
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor
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Time Factors
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Tissue Distribution
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription, Genetic
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Transforming Growth Factor beta*
Substances
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Bmp2 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Cytokines
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DNA-Binding Proteins
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Glial Fibrillary Acidic Protein
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta
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cardiotrophin-like cytokine