HEPATOCYTE GROWTH-FACTOR STIMULATES THE DIFFERENTIATION OF HUMAN TRACHEAL EPITHELIA IN-VITRO

Hepatocyte growth factor (HGF) can influence epithelial cell growth an d differentiation. We examined the actions of recombinant human HGF (r hHGF) 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 inc reases 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 t reated with rhHGF for 48 h showed a significant increase in mediator-i nduced Cl- secretion and a decrease in amiloride-sensitive sodium abso rption. No effect on transepithelial resistance was observed with rhHG F treatment. The enhancement of short-circuit responses by basolateral rhHGF was dose dependent. Our results demonstrate that rhHGF has hype rtrophic actions on, and can influence the differentiation of, human a irway epithelia in vitro, presumably through the activation of c-met a t the basolateral surface of these cells.