TY - JOUR
T1 - BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the wnt/β-catenin signaling pathway
AU - Yang, Jin-Wei
AU - Ma, Wei
AU - Luo, Tao
AU - Wang, Dong-Yan
AU - Lu, Jian-Jun
AU - Li, Xing-Tong
AU - Wang, Tong-Tong
AU - Cheng, Jing-Ru
AU - Ru, Jin
AU - Gao, Yan
AU - Liu, Jia
AU - Liang, Zhang
AU - Yang, Zhi-Yong
AU - Dai, Ping
AU - He, Yong-Sheng
AU - Guo, Xiao-Bing
AU - Guo, Jian-Hui
AU - Li, Li-Yan
PY - 2016/5/4
Y1 - 2016/5/4
N2 - 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.
AB - 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.
KW - BDNF
KW - human neural stem cell
KW - GSK-3beta
KW - Wnt/beta-catenin signaling pathway
UR - http://www.ncbi.nlm.nih.gov/pubmed/27144323
U2 - 10.3109/08977194.2016.1157791
DO - 10.3109/08977194.2016.1157791
M3 - Article
SN - 0897-7194
VL - 34
SP - 19
EP - 32
JO - Growth Factors
JF - Growth Factors
IS - 1-2
ER -