期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 24, 期 1, 页码 23-40出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S1044-7431(03)00082-4
关键词
brain; rat; IGF-I; insulin-like growth factor-I; stem cell; progenitor cell; hippocampus; neurogenesis; MAPK; mitogen-activated protein kinase; P13-K; IGFBP
资金
- NINDS NIH HHS [N01 NS 62348] Funding Source: Medline
The aim of the present study was to investigate the potential direct effects of insulin-like growth factor-I (IGF-I) on adult rat hippocampal stem/progenitor cells (AHPs). IGF-I-treated cultures showed a dose-dependent increase in thymidine incorporation, total number of cells, and number of cells entering the mitosis phase. Pretreatment with fibroblast growth factor-2 (FGF-2) increased the IGF-I receptor (IGF-IR) expression, and both FGF-2 and IGF-I were required for maximal proliferation. Time-lapse recordings showed that IGF-I at 100 ng/ml decreased differentiation and increased proliferation of single AHPs. Specific inhibition of mitogen-activated protein kinase kinase (MAPKK), phosphatidylinositol 3-kinase (PI3-K), or the downstream effector of the PI3-K pathway, serine/threonine p70 S6 kinase (p70(S6K)) showed that both the MAPK and the PI3-K pathways participate in IGF-I-induced proliferation but that the MAPK activation is obligatory. These results were confirmed with dominant-negative constructs for these pathways. Stimulation of differentiation was found at a low dose (1 ng/ml) of IGF-I, clonal analysis indicating an instructive component of IGF-I signaling. (C) 2003 Elsevier Science (USA). All rights reserved.
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