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 nervous system. During development, SCs cease proliferation and differentiate into either a myelin-forming or non-myelin forming mature phenotype. We are interested in the role of insulin-like growth factor-I (IGF-I) in SC development. We have shown previously SCs proliferate in response to IGF-I in vitro. In the current study, we investigated the role 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 decreased proliferation and induced differentiation of SCs. IGF-I enhanced both 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 actions of IGF-I. We examined the expression of IGFBP-5 during SC differentiation. Both cAMP and Matrigel matrix treatment enhanced IGFBP-5 protein expression and cAMP increased IGFBP-5 gene expression five fold. These findings suggest IGF-I potentiates SC differentiation. The concomitant up-regulation of IGFBP-5 may play a role in targeting IGF-I to SCs and thus increase local IGF-I bioavailability.
Cheng
H L
HL
Department of Neurology, University of Michigan, Ann Arbor 48109, USA.
Feldman
E L
EL
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D015152:Blotting, Northern; D016466:CHO Cells / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D006224:Cricetinae; D004338:Drug Combinations; D005109:Extracellular Matrix; D015870:Gene Expression / Q000502:physiology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007797:Laminin / Q000494:pharmacology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012583:Schwann Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects
D001672:Biocompatible Materials; D004338:Drug Combinations; D018975:Insulin-Like Growth Factor Binding Protein 5; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007334:Insulin-Like Growth Factor I; D003094:Collagen