BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the wnt/β-catenin signaling pathway

• Published in: Growth factors (Chur, Switzerland) Switzerland), 2016-01, Vol.34 (1-2), p.19-32
• Main Authors: Yang, Jin-Wei, Ma, Wei, Luo, Tao, Wang, Dong-Yan, Lu, Jian-Jun, Li, Xing-Tong, Wang, Tong-Tong, Cheng, Jing-Ru, Ru, Jin, Gao, Yan, Liu, Jia, Liang, Zhang, Yang, Zhi-Yong, Dai, Ping, He, Yong-Sheng, Guo, Xiao-Bing, Guo, Jian-Hui, Li, Li-Yan
• Format: Article
• Language: English
• Subjects: BDNF; GSK-3β; Human neural stem cell; Wnt/β-catenin signaling pathway
• ISSN: 0897-7194; 1029-2292
• DOI: 10.3109/08977194.2016.1157791

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/β-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3β expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and β-catenin components were all downregulated, whereas GSK-3β was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3′-oxime (BIO), a small molecule inhibitor of GSK-3β. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/β-catenin signaling pathway, and that this interaction may be mediated by GSK-3β.