STIMULATION OF DNA-SYNTHESIS IN HEPATOCYTES BY HEPATOCYTE GROWTH-FACTOR BOUND TO EXTRACELLULAR-MATRIX

Hepatocyte growth factor (HGF) purified from human placenta was specifically bound to a component in ECM secreted from lung fibroblasts, hepatocytes, and nonparenchymal liver cells. HGF was also bound to a component in basement membrane matrigel. The rate of DNA synthesis in hepatocytes cultured on the HGF-bound ECM was 4-7 times that of control hepatocytes. When ECM-coated dishes were pretreated with heparinase and heparitinase prior to binding of HGF, the stimulation decreased remarkably. A considerable decrease in the stimulation was observed following the washing of HGF-bound ECM with 1 M NaCl. We propose, based on these observations, that HGF bound to the ECM component present in Disse's space functions in regeneration following hepatic injury. © 1993 Academic Press, Inc.