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Regulation of Rat Schwann Cell P o Expression and DNA Synthesis by Insulin‐like Growth Factors In Vitro
Author(s) -
Stewart Helen J. S.,
Bradke Frank,
Tabernero Arantxa,
Morrell David,
Jessen Kristjan R.,
Mirsky Rhona
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01240.x
Subject(s) - forskolin , growth factor , biology , fibroblast growth factor , medicine , endocrinology , microbiology and biotechnology , dna synthesis , schwann cell , cellular differentiation , transforming growth factor , platelet derived growth factor , platelet derived growth factor receptor , in vitro , biochemistry , receptor , stimulation , gene
Myelination by Schwann cells is likely to be regulated in Vitro by positive and negative epigenetic factors. In Vitro , the positive regulation of myelin differentiation, in particular expression of the major myelin protein P o , can be mimicked by cAMP elevating agents, while serum, transforming growth factor (TGF)βs, and fibroblast growth factor (FGF)2 have been shown to exert a negative effect on this differentiation. Growth factors which promote P o induction have not, however, been identified previously. Using a forskolin concentration (0.4 μM) which alone produces little P o mRNA or protein induction, we show that insulin‐like growth factor (IGF)‐I, IGF‐II and high concentrations of insulin promote high levels of P o induction, although in the absence of forskolin they have no effect. Another event related to Schwann cell differentiation, induction of galactocerebroside expression in response to cAMP analogues, is also potentiated by IGFs. In a different context, IGFs regulate Schwann cell DMA synthesis. We find that in defined medium forskolin plus FGF2, TGFβ or platelet‐derived growth factor (PDGF) BB causes minimal DNA synthesis in the absence of IGFs and that IGFs act as potent mitogens under these conditions. IGFs also potentiate DNA synthesis induced by β isoforms of neu‐differentiation factors (NDFs), although in this case considerable DNA synthesis occurs even in the absence of IGF. These results show that IGFs can act as powerful stimulators of both proliferation and differentiation in Schwann cells, and that the total growth factor input determines which of these pathways IGFs will promote.