Schwann cells express NDF and SMDF/n-ARIA mRNAs, secrete neuregulin, and show constitutive activation of erbB3 receptors: Evidence for a neuregulin autocrine loop

Claudia Rosenbaum, Saikumar Karyala, Mark A. Marchionni, Haesun A. Kim, Alexei L. Krasnoselsky, Beth Happel, Indu Isaacs, Robert Brackenbury, Nancy Ratner

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Cultured Schwann cells secreted low levels (30 pg/ml/ 1.5 x 106 cells) 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 antineuregulin 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.

Original languageEnglish (US)
Pages (from-to)604-615
Number of pages12
JournalExperimental Neurology
Volume148
Issue number2
DOIs
StatePublished - Dec 1997
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Keywords

  • Autocrine
  • Fibroblast
  • Glial growth factor
  • HGF
  • NDF
  • SMDF
  • Schwann cell
  • TGF-β
  • bFGF

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