Role of neuregulin-1β in the developing lung

Christiane E L Dammann, Heber C. Nielsen, Kermit L. Carraway

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Neuregulins play a critical role in the developing heart, nervous, and mammary systems. Neuregulin-1-induced cardiac, neuronal, and mammary differentiation is based on a cell-cell communication model, where the ligand neuregulin-1 is produced and secreted by one cell type, which does not express its receptors erbB3 and erbB4 and acts on neighboring cell types that do express these receptors. We proposed that neuregulin-1 affects fetal lung maturation through a similar mechanism. Immunostaining showed neuregulin-1 in fetal lung that increased in fibroblasts at the onset of surfactant synthesis. Neuregulin-1β was found to be secreted by the fetal lung fibroblast and stimulated type II cell surfactant synthesis. Both fetal lung fibroblast-conditioned media and neuregulin-1 stimulated erbB2 receptor phosphorylation in type II cells. The effects of neuregulin-1 and of fibroblast-conditioned media on both surfactant synthesis and type II cell erbB2 phosphorylation were specifically blocked by antibody to neuregulin-1. Thus, neuregulin-1β may control fetal lung maturation through mesenchymal-epithelial interactions in a paracrine mechanism similar to that described for the developing heart, brain, and mammary systems.

Original languageEnglish (US)
Pages (from-to)1711-1716
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume167
Issue number12
DOIs
StatePublished - Jun 15 2003

Keywords

  • ErbB receptors
  • Fetal lung development
  • Fibroblast type II cell communication
  • Fibroblast-conditioned medium
  • Fibroblast-pneumocyte factor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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