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.[1]References
- Astrocyte differentiation of fetal neuroepithelial cells involving cardiotrophin-1-induced activation of STAT3. Ochiai, W., Yanagisawa, M., Takizawa, T., Nakashima, K., Taga, T. Cytokine (2001) [Pubmed]
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