Internalization and degradation of hepatocyte growth factor in hepatocytes with down-regulation of the receptor/c-Met.

Hepatocyte growth factor (HGF) promotes proliferation of cultured hepatocytes by its interaction with cell surface receptors. In this paper, we examined the metabolic fate of HGF using hepatocytes. Kinetic analysis using [125I]HGF showed that 40% of surface-bound HGF was rapidly internalized in hepatocytes within 30 min at 37 degrees C. Under these conditions, the amount of HGF-bound c-Met, the high-affinity receptor, decreased from the cell surface. Furthermore, the internalized HGF was degraded and released from the cells. These results indicate that cell surface-bound HGF is internalized and degraded by the receptors, including c-Met, on hepatocytes.