Insulinlike growth factor gene expression in rat muscle during reinnervation

Because insulinlike growth factors (IGFs) support motor axon regeneration, we tested whether the IGF genes expressed during the development of neuromuscular synapses are reexpressed in adult rat muscles during synapse regeneration. Following sciatic nerve crush, IGF-II mRNAs per poly(A)+ RNA, as well as per poly(A)+ RNA per milligram muscle, were significantly up-regulated in denervated relative to intact contralateral gastrocnemius muscles. IGF-II mRNAs were down-regulated after the reestablishment of functional neuromuscular synapses, but remained up-regulated when nerves were transected to prevent the reestablishment of synapses. These data are consistent with a model in which the IGF-II gene is reexpressed during regeneration due to loss of nerve-dependent feedback inhibition. There was a slight but significant increase in IGF-I mRNAs per poly(A)+ RNA per milligram muscle, probably as a consequence of muscle atrophy. These results show that IGF-II gene expression is up-regulated in muscle during the reestablishment of synapses.