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Published ahead of print on March 27, 2003, doi:10.1164/rccm.200205-468OC
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American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 1711-1716, (2003)
© 2003 American Thoracic Society

Original Article

Role of Neuregulin-1ß in the Developing Lung

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

Department of Pediatrics, Division of Newborn Medicine, Tufts University and Floating Hospital for Children; Department of Cell Biology, Harvard Medical School; and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Christiane E. L. Dammann, M.D., Department of Pediatrics, Division of Newborn Medicine, Floating Hospital for Children at Tufts-New England Medical Center, 750 Washington Street, Boston, MA. E-mail: cdammann{at}tufts-nemc.org

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-1ß 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-1ß 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.

Key Words: fetal lung development • fibroblast–pneumocyte factor • fibroblast-conditioned medium • erbB receptors • fibroblast type II cell communication




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