Hepatocyte growth factor and other fibroblast secretions modulate the phenotype of human bronchial epithelial cells

Mike M. Myerburg, Joseph D. Latoche, Erin E. McKenna, Laura P. Stabile, Jill S. Siegfried, Carol A. Feghali-Bostwick, Joseph M. Pilewski

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The luminal airway surface is lined with epithelial cells that provide a protective barrier from the external environment and clear inhaled pathogens from the lung. To accomplish this important function, human bronchial epithelial (HBE) cells must be able to rapidly regenerate a mucociliary layer of cells following epithelial injury. Whereas epithelial-fibroblast interactions are known to modulate the airway architecture during lung development and repair, little is known about how these two cells interact. Using a primary HBE and lung fibroblast coculture system, we demonstrate that 1) subepithelial fibroblasts provide a suitable environment for differentiation of HBE cells into a polarized ciliated phenotype despite being cultured in media that induces terminal squamous differentiation and growth arrest in the absence of fibroblasts, 2) HBE cells cocultured with subepithelial fibroblasts exhibit augmented ciliogenesis, accelerated wound repair, and diminished polarized ion transport compared with cells grown in control conditions, and 3) hepatocyte growth factor (HGF) is important for subepithelial fibroblast modulation of HBE cell differentiation. These results provide a model to study fibroblast modulation of epithelial phenotype and indicate that HGF secreted by subepithelial fibroblasts contributes to HBE cell differentiation.

Original languageEnglish (US)
Pages (from-to)L1352-L1360
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 2007

Keywords

  • Airway epithelium
  • Ciliogenesis
  • Epithelial-mesenchymal interactions
  • Ion transport

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