Insulin-like growth factors and their receptors in muscle development.
Several proteins involved in IGF action are expressed in C2 cells and their abundance was found to vary as a function of development. IGF-I and II mRNA levels rose 10 and 25-fold, respectively, during differentiation, and were accompanied by an increase in growth factor secretion. The accumulation of IGF-II in conditioned culture medium was much greater than that of IGF-I. There was also an increase in the number of IGF-I receptors and IGF-II/CIMPR on the cell surface during differentiation. The sustained rise in IGF-II/CIMPR expression appeared to be a consequence of a similar increase in its mRNA abundance. The mechanisms responsible for the transient increment in IGF-I receptor number were not assessed, although it is likely that the decline in IGF-I receptor content after 72 hours in differentiation medium was a consequence of down-regulation by the IGF-II that accumulated in the medium (35). In contrast to the 13-fold rise in IGF-II/CIMPR mRNA levels, transcript levels for the CDMPR remained constant during C2 cell development, enzymatic activities of two lysosomal enzymes did not change, and only a small increment was detected at a single time point in the expression of several lysosomal enzyme mRNAs. In addition, during C2 muscle differentiation, a novel IGF binding protein was induced. These results demonstrate modulation of several components of IGF signaling pathways in differentiating myoblasts, and argue for a local role for IGFs in muscle development.
Szebenyi
G
G
Washington University School of Medicine, Department of Medicine, St. Louis, MO 63110.
Rotwein
P
P
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002460:Cell Line; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D024510:Muscle Development; D009132:Muscles / Q000166:cytology; D011956:Receptors, Cell Surface / Q000502:physiology*; D017451:Receptors, Somatomedin
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II