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/-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-3 expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and -catenin components were all downregulated, whereas GSK-3 was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3-oxime (BIO), a small molecule inhibitor of GSK-3. 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/-catenin signaling pathway, and that this interaction may be mediated by GSK-3.
基金:
Natural Science Foundation of ChinaNational Natural Science Foundation of China [30960156, 31260253, 31560295]; Priority Union Foundation of Yunnan Provincial Science and Technology Department; Kunming Medical University [2012FB002, 2013FB114]; Special Major Foundation of Education Department of Yunnan Province [ZD2013002]; Science Foundation of Education Department of Yunnan Province [2014C020Y]
第一作者机构:[1]Kunming Med Univ, Inst Neurosci, Yunnan Kunming, Peoples R China;[2]First Peoples Hosp Yunnan Prov, Dept Gen Surg 2, Yunnan Kunming, Peoples R China;
通讯作者:
通讯机构:[1]Kunming Med Univ, Inst Neurosci, Yunnan Kunming, Peoples R China;[2]First Peoples Hosp Yunnan Prov, Dept Gen Surg 2, Yunnan Kunming, Peoples R China;
推荐引用方式(GB/T 7714):
Yang Jin-Wei,Ma Wei,Luo Tao,et al.BDNF promotes human neural stem cell growth via GSK-3-mediated crosstalk with the wnt/-catenin signaling pathway[J].GROWTH FACTORS.2016,34(1-2):19-32.doi:10.3109/08977194.2016.1157791.
APA:
Yang, Jin-Wei,Ma, Wei,Luo, Tao,Wang, Dong-Yan,Lu, Jian-Jun...&Li, Li-Yan.(2016).BDNF promotes human neural stem cell growth via GSK-3-mediated crosstalk with the wnt/-catenin signaling pathway.GROWTH FACTORS,34,(1-2)
MLA:
Yang, Jin-Wei,et al."BDNF promotes human neural stem cell growth via GSK-3-mediated crosstalk with the wnt/-catenin signaling pathway".GROWTH FACTORS 34..1-2(2016):19-32