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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
出版日期2005-06
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
ISSN号0022-3042
DOI10.1111/j.1471-4159.2005.03118.x
文献子类Article
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.
WOS关键词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
WOS研究方向Biochemistry & Molecular Biology ; Neurosciences & Neurology
语种英语
WOS记录号WOS:000229172900018
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/273864]  
专题药理学第二研究室
通讯作者Feng, LY
作者单位1.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Grad Sch, Shanghai Inst Mat Med, Inst Neurosci, Shonghai, Peoples R China
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：上海药物研究所

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