NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway
文献类型:期刊论文
作者 | Jin, L ; Hu, XH ; Feng, LY |
刊名 | JOURNAL OF NEUROCHEMISTRY
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出版日期 | 2005 |
卷号 | 93期号:5页码:1251-1261 |
关键词 | fibroblast growth factor 2 glycogen synthase kinase-3 inhibition neurotrophin 3 proliferation phosphatidylinositol 3-kinase FIBROBLAST-GROWTH-FACTOR CENTRAL-NERVOUS-SYSTEM GLYCOGEN-SYNTHASE KINASE-3 STEM-CELLS PRECURSOR CELLS NEUROTROPHIN RECEPTORS PHOSPHATIDYLINOSITOL 3-KINASE DEVELOPMENTAL EXPRESSION FGF RECEPTORS FACTOR EGF |
ISSN号 | 0022-3042 |
通讯作者 | Feng, LY (reprint author), Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China,lyfeng@sibs.ac.cn |
英文摘要 | Neurotrophin 3 (NT3), a member of the neurotrophin family, antagonizes the proliferative effect of fibroblast growth factor 2 (FGF2) on cortical precursors. However, the mechanism by which NT3 inhibits FGF2-induced neural progenitor (NP) cell proliferation is unclear. Here, using an FGF2-dependent rat neurosphere culture system, we found that NT3 inhibits both FGF2-induced neurosphere growth and bromodeoxyuridine (BrdU) incorporation in a dose-dependent manner. U0126, a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor, and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, both inhibited FGF2-induced BrdU incorporation, suggesting that the extracellular signal-regulated kinase1/2 (ERK1/2) and PI3K pathways are required for FGF2-induced NP cell proliferation. NT3 significantly inhibited FGF2-induced phosphorylation of Akt and glycogen synthase kinase 3 beta (GSK3 beta), a downstream kinase of Akt, whereas phosphorylation of ERK1/2 was unaffected. The inhibitory effect of NT3 on FGF2-induced NP cell proliferation was abolished by LY294002, and treatment with SB216763, a specific GSK3 inhibitor, antagonized the NT3 effect, rescuing both neurosphere growth and BrdU incorporation. Moreover, experiments with anti-NT3 antibody revealed that endogenous NT3 also plays a role in inhibiting FGF2-induced NP cell proliferation, and that anti-NT3 antibody enhanced phospho-Akt and phospho-GSK3 beta levels in the presence of FGF2. These findings indicate that FGF2-induced NP cell proliferation is inhibited by NT3 via the PI3K/GSK3 pathway. |
学科主题 | Biochemistry & Molecular Biology ; Neurosciences & Neurology |
收录类别 | SCI |
语种 | 英语 |
公开日期 | 2012-07-23 |
源URL | [http://ir.sibs.ac.cn/handle/331001/1900] ![]() |
专题 | 上海神经科学研究所_神经所(总) |
推荐引用方式 GB/T 7714 | Jin, L,Hu, XH,Feng, LY. NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway[J]. JOURNAL OF NEUROCHEMISTRY,2005,93(5):1251-1261. |
APA | Jin, L,Hu, XH,&Feng, LY.(2005).NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway.JOURNAL OF NEUROCHEMISTRY,93(5),1251-1261. |
MLA | Jin, L,et al."NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway".JOURNAL OF NEUROCHEMISTRY 93.5(2005):1251-1261. |
入库方式: OAI收割
来源:上海神经科学研究所
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