title: IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle.
abstract: Secreted peptide growth factors are critical extracellular signals that interact to promote the proliferation, differentiation, and survival of progenitor cells in developing tissues. IGF-I signaling through the IGF type I receptor provides a mitogenic signal for numerous cell types, including stem and progenitor cells. We have utilized the O-2A oligodendrocyte progenitor to study the mechanism of IGF-I mitogenic actions since these progenitors respond to IGF-I in vitro, and gene targeting studies in mice have demonstrated that IGF-I is essential for normal oligodendrocyte development in vivo. The goal of this study was to elucidate the mechanism by which IGF-I promotes the proliferation of oligodendrocyte progenitors in the context of other mitogens critical for their proliferation. Results presented here show that IGF-I significantly amplified the actions of FGF-2 and PDGF to promote DNA synthesis in O-2A progenitors. Investigation of cell cycle kinetics revealed that IGF-I had no significant effect on the rate of cell cycle progression. Instead, IGF-I promoted increased recruitment of O-2A progenitors into the S phase of the cell cycle. These studies support a role for IGF-I as a cell cycle progression factor for progenitor cells.
authors.affiliation: Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: T J
authors.initials: TJ
authors.lastname: Frederick
authors.forename: T L
authors.initials: TL
authors.lastname: Wood
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D007700:Kinetics; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage; D051381:Rats; D016196:S Phase / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D004247:DNA; D001973:Bromodeoxyuridine