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Insulin‐like growth factor I: A mitogen for rat schwann cells in the presence of elevated levels of cyclic AMP
Author(s) -
JungTestas Ingrid,
Robel Paul,
Baulieu EtienneEmile,
Schumacher Michael
Publication year - 1993
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.440080403
Subject(s) - forskolin , biology , epidermal growth factor , growth factor , autocrine signalling , schwann cell , medicine , endocrinology , receptor , insulin like growth factor , microbiology and biotechnology , biochemistry , stimulation
Abstract To develop effective procedures for improving the regeneration of peripheral nerves and for preventing the formation of neurofibromas, it is necessary to identify the different mitogens that stimulate the proliferation of Schwann cells. Insulinlike growth factor I (IGF‐I), which is a potent autocrine growth factor in many tissues, is synthesized by proliferating Schwann cells. However, the role of IGF‐I in stimulating their division is still uncertain. Here we show that nanomolar concentrations of IGF‐I stimulate the growth of Schwann cells in primary culture. IGF‐I alone was uneffective but in the presence of forskolin (5 μM) or dibutyryl cyclic AMP (dbcAMP, 10 μM), it became a potent mitogen. Neither IGF‐II nor epidermal growth factor (EGF) were effective, even in the presence of forskolin. Insulin also stimulated Schwann cell proliferation in the presence of forskolin, but only at micromolar concentration. Receptors for IGF‐I were visualized on the Schwann cell surface by indirect immunofluorescence staining using anti‐human IGF‐I receptor antibodies. Their presence was also assessed by binding assays using [ 125 I]‐IGF‐I as a ligand. Scatchard analysis showed a single class of high‐affinity receptors (K d = 1.5 nM). Competition studies with unlabeled IGF‐I or insulin indicated a half‐maximal displacement of [ 125 I]‐IGF‐I by IGF‐I at about 5 nM, while insulin was about 500‐fold less effective. The number of binding sites for IGF‐I was increased by exposing cells for 3 days to forskolin (‐ forskolin: about 5,100; + forskolin: about 12,200 binding sites/cell). These results suggest that forskolin increases available receptors for IGF‐I, which is consistent with the synergism between cAMP and IGF‐I in stimulating Schwann cell growth. © 1993 Wiley‐Liss, Inc.