HGF is an autocrine growth factor for skeletal muscle satellite cells in vitro

Muscle satellite cell activation following injury is essential for muscle r epair, and hepatocyte growth factor/scatter factor (HGF) was the first grow th factor shown to be able to stimulate activation and early division of ad ult satellite cells in culture and in muscle tissue. In addition, HGF was s hown to be present in uninjured and injured skeletal muscle. Experiments in this report demonstrate that cultured satellite cells also synthesize and secrete HGF. Reverse transcription-polymerase chain reaction (RT-PCR) was u sed to demonstrate the presence of HGF mRNA in cultured adult satellite cel ls as early as 12 h from the time of plating. Message content was detectabl e at early times in culture and appeared to increase between 36 and 48 h. H GF protein expression was demonstrated during this time period by immunoflu orescence localization; HGF was localized to mononucleated cells and multin ucleated myotubes, HGF message was not detectable in muscle-derived fibrobl ast clones, and fibroblast-like cells in satellite cell cultures were negat ive for HGF by immunofluorescence analysis. Furthermore, Western blot analy sis revealed the presence of HGF in satellite cell culture conditioned medi um, associated with the cell surface and inside cells. Finally, the additio n of neutralizing HGF antibodies during the proliferation phase in culture (42-90 h) significantly reduced cell proliferation. These experiments indic ate that HGF is expressed by cultured satellite cells and that endogenous H GF from satellite cells can act in an autocrine fashion. Because HGF plays a central role in satellite cell activation, it is likely that direct admin istration of HGF into damaged muscle may represent a potentially useful app roach for stimulating muscle repair. This approach may also be useful in en hancing the efficiency of myoblast transplantation in vivo. (C) 2000 John W iley & Sons, Inc.