Characterization of insulin-like growth factor-I and its receptor and binding proteins in transected nerves and cultured schwann cells

Hsin Lin Cheng, Ann Randolph, Douglas Yee, Patrick Delafontaine, Gihan Tennekoon, Eva L. Feldman

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)525-536
Number of pages12
JournalJournal of Neurochemistry
Volume66
Issue number2
DOIs
StatePublished - Feb 1996

Keywords

  • Binding protein
  • Insulin-like growth factor
  • Nerve transection
  • Receptor
  • Schwann cells

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