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Insulin‐like growth factor‐binding protein 6 inhibits survival and differentiation of rat oligodendrocyte precursor cells
Author(s) -
Kühl Nicole M.,
Hoekstra Dick,
De Vries Hans,
De Keyser Jacques
Publication year - 2003
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10263
Subject(s) - oligodendrocyte , biology , growth factor , endocrinology , medicine , remyelination , insulin like growth factor , basic fibroblast growth factor , myelin basic protein , precursor cell , microbiology and biotechnology , insulin like growth factor binding protein , lineage markers , myelin , cell , stem cell , receptor , progenitor cell , central nervous system , biochemistry
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. © 2003 Wiley‐Liss, Inc.