Hepatocyte growth factor promotes growth and lumen formation of fetal lung epithelial cells in primary culture

Mesenchyme-epithelium interactions are generally considered critical for fetal lung development. Hepatocyte growth factor (HGF), a mesenchyme-derived mitogen active on a variety of epithelial cells, appears to be involved in the morphogenesis of fetal liver and kidney. During lung development, HGF and its receptor, c-Met, are expressed in close proximity in mesenchymal cells and epithelial cells, respectively. To examine the role of HGF in fetal lung development, we investigated the effects of HGF on lung epithelial cells derived from a 15-day-old mouse fetus. First, HGF induces a 45% increase in [3H]thymidine incorporation and a 65% increase in cell number by crystal violet analysis at 10 ng/mL concentration, and the increase is dose dependent. Second, HGF facilitates the formation of an organotypic arrangement of the fetal epithelial cells on a basement membrane extract (Matrigel) that resembles alveolar structures in vivo, and the maximum increase is about twice the control level at 10 ng/mL. These results suggest that HGF may be implicated in fetal lung development through the regulation of mesenchyme-epithelium interactions.