THE MESSENGER-RNAS ENCODING ACIDIC FGF, BASIC FGF AND FGF RECEPTOR ARE COORDINATELY DOWN-REGULATED DURING MYOGENIC DIFFERENTIATION

Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that exert pleiotropic effects in a range of cell types including skeletal myocytes. Previous studies demonstrate that exogenously supplied FGFs stimulate proliferation of myoblasts and inhibit their differentiation in culture, but little information is available concerning endogenous expression of FGFs by skeletal myocytes. In this study acidic and basic FGF mRNAs were found to be expressed in murine and rat skeletal muscle, and expression was demonstrated to vary with the tissue and species examined. Myogenic cell lines were then analyzed to determine if FGFs are expressed in myoblasts, and if so, whether expression is regulated during myogenic differentiation. Murine Sol 8 and rat L6 myoblasts were found to express acidic and basic FGF mRNAs, and the expression of both growth factors was downregulated at the transcriptional level during myogenic differentiation. A decrease in expression of the mouse homologue of the human FGF receptor paralleled the decrease in acidic and basic FGF mRNAs in Sol 8 cells, indicating that the decrease in FGF receptor abundance previously observed during myogenic differentiation is regulated at the mRNA level. The results of this study suggest that a coordinate decrease in endogenously produced acidic and basic FGFs and their cognate receptor may participate in the regulation of myogenic differentiation. Furthermore, the observation that expression of a myogenic determination gene, myogenin, increases as FGF transcripts decline, together with previous data demonstrating suppression of myogenin expression by FGF, suggest a mechanism whereby endogenously produced FGFs may exert their effect on differentiation.