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Schwann Cells Express NDF and SMDF/n-ARIA mRNAs, Secrete Neuregulin, and Show Constitutive Activation of erbB3 Receptors: Evidence for a Neuregulin Autocrine Loop

Authors
Journal
Experimental Neurology
0014-4886
Publisher
Elsevier
Publication Date
Volume
148
Issue
2
Identifiers
DOI: 10.1006/exnr.1997.6696
Keywords
  • Glial Growth Factor
  • Bfgf
  • Hgf
  • Tgf-β
  • Schwann Cell
  • Ndf
  • Autocrine
  • Fibroblast
  • Smdf
Disciplines
  • Biology

Abstract

Abstract Cultured Schwann cells secreted low levels (30 pg/ml/1.5 × 10 6cells) of a 45-kDa neuregulin protein and showed constitutive activation of a neuregulin receptor, Erb-B3, suggesting the existence of an autocrine loop involving neuregulins in Schwann cells. RT-PCR analyses indicated that Schwann cells and fibroblasts in culture produced SMDF/n-ARIA and NDF but not GGF neuregulin messages. Schwann cell and fibroblast neuregulin messages encoded both β and α domains; Schwann cell transcripts encoded only transmembrane neuregulin forms while fibroblast messages encoded transmembrane and secreted forms. SMDF/n-ARIA and NDF messages were also expressed in early postnatal rat sciatic nerve, suggesting a role for neuregulins in peripheral nerve development. An anti-neuregulin antibody inhibited the mitogenic response of Schwann cells to cultured neurons and to extracts of cultured neurons or embryonic brain, consistent with the accepted paracrine role of neuregulins on Schwann cells. Surprisingly, the same antibody inhibited Schwann cell proliferation stimulated by several unrelated mitogens including bFGF, HGF, and TGF-β1. These data implicate both paracrine and autocrine pathways involving neuregulin form(s) in Schwann cell mitogenic responses.

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