Insulin-like growth factor-binding protein 6 inhibits survival and differentiation of rat oligodendrocyte precursor cells.
Insulin-like growth factor 1 (IGF-1) is a growth and survival factor for oligodendrocyte lineage cells and promotes myelination. We demonstrate that IGF-binding protein 6 (IGFBP-6) is expressed and localized to the Golgi complex in rat oligodendrocyte precursor (O2A) cells. IGFBP-6 mRNA showed a developmentally regulated expression pattern, displaying a transient decrease during early development, and enhanced levels upon cell maturation. IGFBP-6 mRNA expression could be reduced by addition of basic fibroblast growth factor and progesterone while estrogen increased IGFBP-6 mRNA. IGF-1, platelet-derived growth factor, and insulin had no effect. When added exogenously, IGFBP-6 reduced O2A cell survival in the absence of IGF-1 and inhibited IGF-1-stimulated survival in a partially IGF-1-dependent and partially IGF-1-independent fashion. In addition, IGFBP-6 reduced the IGF-stimulated expression of two myelin proteins, CNPase and MAG. Taken together, the data show that IGFBP-6 is a new negative effector of oligodendrocyte survival and differentiation.
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*
D006131:Growth Inhibitors; D018976:Insulin-Like Growth Factor Binding Protein 6; D018992:Myelin-Associated Glycoprotein; D012333:RNA, Messenger; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases