Hepatocyte growth factor stimulates the differentiation of human tracheal epithelia in vitro

Hepatocyte growth factor (HGF) can influence epithelial cell growth and differentiation. We examined the actions of recombinant human HGF (rhHGF) on the differentiation of human primary tracheal epithelial (HTE) cells cultured in vitro for up to 96 h. Basolateral, but not apical, treatment of confluent HTE cell sheets for 48 h with rhHGF led to increases in cell height, cell volume, cilia, and total protein content. Basolateral rhHGF treatment produced a decrease in HGF receptor (c-met) expression but had no effect on c-met mRNA levels. HTE cell sheets treated with rhHGF for 48 h showed a significant increase in mediator-induced Cl- secretion and a decrease in amiloride-sensitive sodium absorption. No effect on transepithelial resistance was observed with rhHGF treatment. The enhancement of short-circuit responses by basolateral rhHGF was dose dependent. Our results demonstrate that rhHGF has hypertrophic actions on, and can influence the differentiation of, human airway epithelia in vitro, presumably through the activation of c-met at the basolateral surface of these cells.