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

Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania Submitted 25 August 2006 ; accepted in final form 14 February 2007 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. airway epithelium; ion transport; epithelial-mesenchymal interactions; ciliogenesis Address for reprint requests and other correspondence: J. M. Pilewski, Division of PACCM, Univ. of Pittsburgh Medical Center, 628 NW Montefiore Univ. Hospital, 3459 Fifth Ave., Pittsburgh, PA 15213 (e-mail: pilewskijm{at}upmc.edu )