title: BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the wnt/β-catenin signaling pathway.
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.
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .|b Second Department of General Surgery, First People's Hospital of Yunnan Province , Yunnan Kunming , China .
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: Yang
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Wang
authors.affiliation: c Department of Anatomy and Biomedical Sciences , Monash University , Melbourne , Australia .
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Lu
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Xing-Tong
authors.initials: XT
authors.lastname: Li
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Tong-Tong
authors.initials: TT
authors.lastname: Wang
authors.affiliation: b Second Department of General Surgery, First People's Hospital of Yunnan Province , Yunnan Kunming , China .
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Cheng
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .|b Second Department of General Surgery, First People's Hospital of Yunnan Province , Yunnan Kunming , China .
authors.forename: Jin
authors.initials: J
authors.lastname: Ru
authors.affiliation: d Department of Pathology , Children's Hospital of Kunming City , Yunnan Kunming , China , and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: b Second Department of General Surgery, First People's Hospital of Yunnan Province , Yunnan Kunming , China .
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Zhang
authors.initials: Z
authors.lastname: Liang
authors.affiliation: e Department of Neurosurgery , First Affiliated Hospital of Kunming Medical University , Yunnan Kunming , China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: He
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Guo
authors.affiliation: b Second Department of General Surgery, First People's Hospital of Yunnan Province , Yunnan Kunming , China .
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Guo
authors.affiliation: a Institue of Neuroscience, Kunming Medical University , Yunnan Kunming , China .
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Li
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000502:physiology; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C489740:FZD1 protein, human; D051157:Frizzled Receptors; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta
keywords: BDNF; GSK-3β; Human neural stem cell; Wnt/β-catenin signaling pathway