Characterization of Insulin‐Like Growth Factor‐I and Its Receptor and Binding Proteins in Transected Nerves and Cultured Schwann Cells

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Abstract
The insulin‐like growth factors (IGFs) are trophic factors whose growth‐promoting actions are mediated via the IGF‐I receptor and modulated by six IGF binding proteins (IGFBPs). In this study, we observed increased transcripts of both IGF‐I and IGF‐I receptor after rat sciatic nerve transection. Schwann cells (SCs) were the main source of IGF‐I and IGFBP‐5 immunoreactivity until 7 days after nerve transection, when invading macrophages in the distal nerve stumps were strongly IGF‐I positive. In vitro, IGF‐I promoted SC mitogenesis. Northern analysis revealed that SCs expressed IGF‐I receptor and IGFBP‐5. IGF‐I treatment increased the intensity of IGFBP‐5 without affecting gene expression. Des(1–3)IGF‐I, an IGF‐I analogue with low affinity for IGFBP, had no such effect. Incubation of recombinant human IGFBP‐5 with SC conditioned media revealed IGF‐I protection of IGFBP‐5 from proteolysis, implying the presence of an IGFBP‐5 protease in SC conditioned media. Collectively, these data support the concept that, in response to nerve injury, invading macrophages produce IGF‐I and SC express the IGF‐I receptor, to facilitate regeneration. This regenerative process may be augmented further by the ability of SC to secrete IGFBPs, which in turn may increase local IGF‐I bioavailability.

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