IGF-I has a direct proliferative effect in adult hippocampal progenitor cells.
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.
Aberg
Maria A I
MA
The Arvid Carlsson Institute for Neuroscience at the Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg University, Blå Stråket 7, SE-413 45 Göteborg, Sweden.
Aberg
N David
ND
Palmer
Theo D
TD
Alborn
Ann-Marie
AM
Carlsson-Skwirut
Christine
C
Bang
Peter
P
Rosengren
Lars E
LE
Olsson
Torsten
T
Gage
Fred H
FH
Eriksson
Peter S
PS
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D018969:Insulin-Like Growth Factor Binding Proteins; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D013936:Thymidine