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Title: NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway
Author: Jin, L ; Hu, XH ; Feng, LY
Source: JOURNAL OF NEUROCHEMISTRY
Issued Date: 2005
Volume: 93, Issue:5, Pages:1251-1261
Keyword: 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
Subject: Biochemistry & Molecular Biology ; Neurosciences & Neurology
Corresponding Author: 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
English Abstract: 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.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1900
Appears in Collections:神经所(总)_期刊论文

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Jin, L; Hu, XH; Feng, LY.NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway,JOURNAL OF NEUROCHEMISTRY,2005,93(5):1251-1261
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