Astrocyte differentiation of fetal neuroepithelial cells involving cardiotrophin-1-induced activation of STAT3.
Cardiotrophin-1 (CT-1) belongs to the interleukin (IL-)6 family of cytokines that share membrane glycoprotein 130 (gp130) as a receptor component critical for signal transduction. We here observed that CT-1 was expressed in mouse fetal neuroepithelial cells, and was capable of inducing astrocyte differentiation from these cells in a synergistic manner with bone morphogenetic protein (BMP)-2, whose expression was also found in the fetal brain. CT-1-induced astrocyte differentiation was solely gp130-dependent. CT-1-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 gp130-downstream transcription factor, signal transducer and activator of transcription 3(STAT3), or by introduction of a mutation in a single STAT3-binding site in the promoter, suggesting a critical role of STAT3 in the CT-1-induced GFAP transcription. These results suggest that astrocyte differentiation in the developing brain involves CT-1-signaling which cooperates with BMP2.
Ochiai
W
W
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
Yanagisawa
M
M
Takizawa
T
T
Nakashima
K
K
Taga
T
T
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D001921:Brain / Q000196:embryology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D019000:Phosphotyrosine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D019000:Phosphotyrosine; C092073:cardiotrophin 1