Recently, it has been demonstrated that functional muscle regeneration occurs with combined delivery of angiogenesis and myogenesis factors. Although this new approach simultaneously targets distinct aspects of the regenerative process, the temporal relationship between myogenesis and angiogenesis during muscle regeneration is not fully characterized. Thus, we examined the expression of several important molecules that regulate myogenesis and angiogenesis following chemically-induced muscle injury. MRFs (MyoD and myogenin) exhibited strong increase in day 5 and returned to the control level by day 14. HIF-1α protein increased to a peak at day 5 and then VEGF protein increased to a peak at day 7. VEGF receptors (Flt-1, KDR/Flk-1, neuropilin-1) protein increased to a peak between 7 and 14 days. Moreover, we examined the effects of inhibition of VEGF signaling with selective VEGF receptor inhibitors, SU1498, on muscle regeneration. The skeletal muscles forced to regenerate in the presence of SU1498 were of poor repair with small regenerating myoﬁbers and increased connective tissues. These results suggest that myogenic and angiogenic pathways are sequentially activated during postnatal muscle regeneration and angiogenesis plays an important role in the success of muscle regeneration.
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