Insulin-like growth factor I: A mitogen for rat schwann cells in the presence of elevated levels of cyclic AMP

✍ Scribed by Ingrid Jung-Testas; Paul Robel; Etienne-Emile Baulieu; Dr. Michael Schumacher

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 944 KB
• Volume: 8
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.440080403

✦ Synopsis

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 pM) or dibutyryl cyclic AMP (dbcAMP, 10 FM), it became a potent mitogen. Neither IGF-I1 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 [12511-IGF-I as a ligand. Scatchard analysis showed a single class of high-affinity receptors (Kd 1.5 nM). Competition studies with unlabeled IGF-I or insulin indicated a half-maximal displacement of L1"I1-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 sitedcell). 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. o 1993 WiIey-Liss, Inc.