HEPATOCYTE GROWTH-FACTOR ACTIVATES QUIESCENT SKELETAL-MUSCLE SATELLITE CELLS IN-VITRO

The effect of hepatocyte growth factor (HGF) on the activation of quie scent rat skeletal muscle satellite cells was evaluated in vitro. Sate llite cells from 9-month-old adult rats are quiescent in vivo and when cultured, display a protracted lag phase prior to division that is no t present in satellite cells from neonatal or regenerating muscle. Und er normal growth conditions, satellite cells divide for the first time between 42 and 60 hr. Hepatocyte growth factor increased proliferatio n in a dose-dependent fashion prior to 48 hr with half-maximal stimula tion at approximately 3 ng/ml; in addition, heparin enhanced this acti vity. The time course of cyclin-D1 and proliferating cell nuclear anti gen (PCNA) expression was accelerated in HGF-treated satellite cells, indicating that cells entered the cell cycle earlier. No significant e ffects on muscle-derived fibroblast proliferation was observed. The si gnalling receptor for HGF is the product of the c-met protooncogene, a nd rtPCR analysis of satellite cells 0-72 hr in culture demonstrated t he presence of this message throughout this time period. The presence of c-met in quiescent satellite cells, the ability of HGF to stimulate precocious entry into the cell cycle, and the previously described lo calization of HGF message in regenerating muscle (Jennische et al., 19 93) indicate that HGF could act as an activator of quiescent satellite cells in vivo. (C) 1995 Wiley-Liss, Inc.