Skeletal muscle satellite cell proliferation in response to members of the fibroblast growth factor family and hepatocyte growth factor.

Abstract

Fibroblast growth factors (FGF) have the ability to regulate satellite cell proliferation in culture and in muscle tissue, but the specific FGF receptors (FGFR) expressed by adult rat muscle satellite cells and the action of members of the FGF family have not been assessed. Therefore, the expression of FGF receptors 1-4 was examined in proliferating satellite cells in culture, and the effects of eight members of the fibroblast growth factor family (FGFs1, 2, 4, 5, 6, 7, 8, and 9) on adult rat muscle satellite cells were evaluated. In addition, the interactions of FGFs with hepatocyte growth factor (HGF) were described. Of the eight FGFs evaluated, 1, 2, 4, 6, and 9 significantly (P < 0.05) stimulated proliferation above control. FGFs5, 7, and 8 displayed no mitogenic activity. Furthermore, combinations of HGF with FGFs2, 4, 6, or 9 stimulated satellite cell proliferation above that of optimal concentrations of HGF alone. Expression of four FGFR genes was detected in satellite cell cultures by reverse-transcription-polymerase chain reaction (RT-PCR). FGFR1 and FGFR4 were the most prominent forms expressed, and FGFR2 was only expressed at low levels. FGFR3 was difficult to detect. FGFR1 and FGFR2 were also expressed in muscle-derived fibroblasts, but FGFR4 and FGFR3 were not. In proliferating cultures of satellite cells, HGF, insulin-like growth factor I (IGF-I) and FGF1 stimulated significantly (P < 0.05) higher levels of FGFR1 message content, relative to control conditions, and platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor (IGF-II) significantly (P < 0.05) depressed FGFR1 expression. During the activation period of satellite cell growth in culture (0-48 h), FGFR1 message content significantly (P < 0.05) increased from less than 1,000 copies per cell to approximately 5,000 copies per cell between 18 and 48 h, and HGF treatment significantly (P < 0.05) accelerated the accumulation of FGFR1 message during this period.