| First Author | Yuan X | Year | 2020 |
| Journal | Neuroscience | Volume | 448 |
| Pages | 219-233 | PubMed ID | 32860934 |
| Mgi Jnum | J:299666 | Mgi Id | MGI:6501343 |
| Doi | 10.1016/j.neuroscience.2020.08.018 | Citation | Yuan X, et al. (2020) Interferon-gamma Facilitates Neurogenesis by Activating Wnt/beta-catenin Cell Signaling Pathway via Promotion of STAT1 Regulation of the beta-Catenin Promoter. Neuroscience 448:219-233 |
| abstractText | Interferon-gamma (IFN-gamma) is critical for central nervous system (CNS) functions and it may be a promising treatment to stimulate CNS regeneration. However, previous studies reported inconsistent results, and the molecular mechanisms remain controversial. Here we show that IFN-gamma-treated mice via intraperitoneal injection have elevated IFN-gamma level in central hippocampus and superior cognitive behaviors IFN-gamma could activates the level of protein expression of Wnt7a, beta-catenin, and CyclinD1 in Wnt/beta-catenin signaling pathway of mice hippocampus. Functional and mechanism analysis in vitro revealed that IFN-gamma promoted the proliferation and differentiation in primary cultured neural stem cells (NSCs). STAT1 was accountable for IFN-gamma-induced activation of the beta-catenin promoter, and IFN-gamma increased the binding affinity of STAT1 to beta-catenin promoter based on luciferase activity and chromatin immunoprecipitation. Our results suggest that IFN-gamma exerts many effects ranging from cognitive function in vivo to NSC proliferation, self-renewal, and differentiation in vitro. It does so by recruiting STAT1 to the beta-catenin promoter, enhancing cis-regulation by STAT1, and ultimately activating Wnt/beta-catenin signaling. In this study, we first found that STAT1 was recruited into the promoter of beta-catenin to activate beta-catenin expression, and this effect was regulated by IFN-gamma. It is also discovered firstly that Wnt/beta-catenin and JAK/STAT pathways form cross-links through STAT1. Promoting neurogenesis through immune stimulation might be a promising strategy for repairing the diseased/injured CNS. This study provides a scientific basis for immunomodulation to promote nerve regeneration and offer a new therapeutic direction for central nervous system regeneration. |
