Muscle differentiation: insulin-like growth factors as positive modulators of myogenic regulatory genes?

The contribution of autocrine production of insulin-like growth factor II (IGFII) to myogenic differentiation was studied in the mouse myogenic C2 cells. Permissive C2 cells were stably transfected with a vector generating antisense RNA complementary to IGF RNAs. Our results show that: (1) accumulation of IGFII mRNA is dramatically decreased (this mRNA is undetectable by RNA blotting); (2) accumulation of MyoD mRNA also becomes undetectable by RNA blot analysis; (3) the ability of the cells to differentiate, including the activation of myogenin and myosin genes, is severely compromised; (4) expression of the MyoD genes and the ability to differentiate are restored following the addition of insulin or IGF to the cells. Our observations indicate that the autonomous differentiation of myogenic cells requires autocrine production of IGF and raise the possibility that IGFII positively regulates expression of the MyoD gene, one of the members of the myogenic regulatory factor family.