BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the wnt/β-catenin signaling pathway. (2nd January 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Growth factors. Volume 34:Number 1/2(2016:Feb.)
• Page Start: 19
• Page End: 32
• Publication Date: 2016-01-02
• Subjects: BDNF -- Human neural stem cell -- GSK-3β -- Wnt/β-catenin signaling pathway; Growth factors -- Periodicals; Physiology -- Periodicals; 611
• DOI: 10.3109/08977194.2016.1157791
• Languages: English
• ISSNs: 0897-7194

Abstract

Abstract: 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.