Signaling crosstalk underlying synergistic induction of astrocyte differentiation by BMPs and IL-6 family of cytokines.
We here show that bone morphogenetic protein (BMP) 7 acted in synergy with the distinct type of cytokines, leukemia inhibitory factor (LIF) and interleukin (IL) 6 that are in the IL-6 family, to induce astrocyte differentiation from neuroepithelial cells as assessed by expression of glial fibrillary acidic protein (GFAP). In this synergistic action, transcription factors, Smads and STAT3 (for signal transducer and activator of transcription 3) activated by respective group of cytokines, as well as a transcriptional coactivator p300 were essential. Taken together with our previous finding that the synergistic astrocyte induction by BMP2 and LIF is attributed to the complex formation of Smads and STAT3 bridged by p300, it is conceivable that this complex formation is a mechanism utilized in common by two different types of cytokines belonging to the BMP and IL-6 families in order to synergistically induce astrocyte differentiation.
Yanagisawa
M
M
Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo, Japan.
Nakashima
K
K
Takizawa
T
T
Ochiai
W
W
Arakawa
H
H
Taga
T
T
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D050881:E1A-Associated p300 Protein; D004847:Epithelial Cells / Q000378:metabolism; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D051905:Smad6 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D012313:RNA; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse