Actions of transforming growth factor‐β on muscle cells

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Abstract
It has recently been reported by three laboratories that transforming growth factor-β (TGF-β) is a potent and reversible inhibitor of differentiation in myogenic cells. To improve our understanding of this inhibition, we investigated the effects of TGF-β on several other processes in L6 myoblasts, with emphasis on actions of the insulin-like hormones (which stimulate myoblast differentiation). We found that TGF-β had no effect on the binding of insulin-like growth factors (IGFs) to their receptors on the cell surface, and it had little or no effect on some actions of the IGFs. There was essentially no change in the suppression of proteolysis or the stimulation of cell proliferation by IGFs when TGF-β was also added to the medium. However, there was an effect of TGF-β on another process stimulated by the IGFs; TGF-β was an equally active and more potent stimulator of amino acid uptake than was IGF-I, and the stimulation was additive beyond the maximal response attained with IGF-I, suggesting that the two act by different mechanisms. TGF-β had significant effects on myoblast morphology, causing the formation of abundant stress fibers containing cytoplasmic (but not myofibrillar) actin. Addition of TGF-β at various times after initiation of differentiation demonstrated that TGF-β inhibits an early process in differentiation. Thus it appears that the interactions of TGF-β and the IGFs in myoblasts are complex; in some instances the effects of IGFs are inhibited and in others they are mimicked or are unaffected. It is clear that TGF-β does not act by simply interfering with IGF binding or blocking early steps in its action on myoblasts.