INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND IGF BINDING PROTEIN-5 IN SCHWANN-CELL DIFFERENTIATION

Schwann cells (SCs) are the myelin producing cells of the peripheral n ervous system. During development, SCs cease proliferation and differe ntiate into either a myelin-forming or non-myelin forming mature pheno type. We are interested in the role of insulin-like growth factor-I (I GF-I) in SC development. We have shown previously SCs proliferate in r esponse to IGF-I in vitro. In the current study, we investigated the r ole of IGF-I in SC differentiation. SC differentiation was determined by morphological criteria and expression of myelin proteins. Addition of 1 mM 8-bromo cyclic AMP (cAMP) or growth on Matrigel matrix decreas ed proliferation and induced differentiation of SCs. IGF-I enhanced bo th cAMP and Matrigel matrix-induced SC differentiation, as assessed by both morphological criteria and myelin gene expression. Cultured SCs also express IGF binding protein-5 (IGFBP-5), which can modulate the a ctions of IGF-I. We examined the expression of IGFBP-5 during SC diffe rentiation. Both cAMP and Matrigel matrix treatment enhanced IGFBP-5 p rotein expression and cAMP increased IGFBP-5 gene expression five fold . These findings suggest IGF-I potentiates SC differentiation. The con comitant up-regulation of IGFBP-5 may play a role in targeting IGF-I t o SCs and thus increase local IGF-I bioavailability. (C) 1997 Wiley-Li ss, Inc.