Figure 2.

Positive feedback mechanism of the astrocytic ET_B receptor signal through activation of Stat3. Activation of astrocytic ET_B receptors stimulates the transcription of cyclin D1, S-phase kinase-associated protein 2 (Skp2), and GFAP through Stat3. Increases in cyclin D1, skp2m, and GFAP proteins are involved in proliferation and hypertrophy associated with phenotype conversion to reactive astrocytes. Activated Stat3 also promotes transcription of ET_B receptors. The upregulation of ET_B receptors results in enhancement in Stat3-mediated gene expression in astrocytes.