Actions of transforming growth factor-beta on muscle cells.
It has recently been reported by three laboratories that transforming growth factor-beta (TGF-beta) is a potent and reversible inhibitor of differentiation in myogenic cells. To improve our understanding of this inhibition, we investigated the effects of TGF-beta on several other processes in L6 myoblasts, with emphasis on actions of the insulin-like hormones (which stimulate myoblast differentiation). We found that TGF-beta 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-beta was also added to the medium. However, there was an effect of TGF-beta on another process stimulated by the IGFs; TGF-beta 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-beta had significant effects on myoblast morphology, causing the formation of abundant stress fibers containing cytoplasmic (but not myofibrillar) actin. Addition of TGF-beta at various times after initiation of differentiation demonstrated that TGF-beta inhibits an early process in differentiation. Thus it appears that the interactions of TGF-beta 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-beta does not act by simply interfering with IGF binding or blocking early steps in its action on myoblasts.
Florini
J R
JR
Biology Department, Syracuse University, New York 13244.
Ewton
D Z
DZ
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006133:Growth Substances / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D015291:Transforming Growth Factors
D000596:Amino Acids; D006133:Growth Substances; D010455:Peptides; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors