Regulation of myogenic differentiation by type β transforming growth factor

Type β transforming growth factor (TGFβ) has been shown to be both a positive and negative regulator of cellular proliferation and differentiation. The effects of TGFβ also are cell-type specific and appear to be modulated by other growth factors. In the present study, we examined the potential of TGFβ for control of myogenic differentiation. In mouse C-2 myoblasts, TGFβ inhibited fusion and prevented expression of the muscle-specific gene products, creatine kinase and acetylcholine receptor. Differentiation of the nonfusing muscle cell line, BC₃H1, was also inhibited by TGFβ in a dose-dependent manner (ID₅₀ ~0.5 ng/ml). TGFβ was not mitogenic for either muscle cell line, indicating that its inhibitory effects do not require cell proliferation. Inhibition of differentiation required the continual presence of TGFβ in the culture media. Removal of TGFβ led to rapid appearance of muscle proteins, which indicates that intracellular signals generated by TGFβ are highly transient and require continuous occupancy of the TGFβ receptor. Northern blot hybridization analysis using a muscle creatine kinase cDNA probe indicated that TGFβ inhibited differentiation at the level of muscle-specific mRNA accumulation. These results provide the first demonstration that TGFβ is a potent regulator of myogenic differentiation and suggest that TGFβ may play an important role in the control of tissue-specific gene expression during development.