High intensity exercise-induced muscle damage: The role of growth factorsSkeletal muscle damage results in increased expression of insulin-like growth factor-1 (IGF-1), which has been associated both with mitogenic and myogenic mechanisms involved in muscle regeneration. Different IGF-1 isoforms (IGF-1Ea, IGF-1Eb and MGF) have been proposed to have varying functions in muscle repair and growth. To gain insight into the potentially differential actions of IGF-1 isoforms in the regulation of muscle regeneration, the time course of their expressions was assessed, at both mRNA and protein levels, after exercise-induced muscle damage in humans. In addition, synthetic MGF E peptide signalling has been characterized in C2C12 myoblasts, in vitro. Changes in muscle's mechanical properties and inflammatory-related factors in the blood associated with muscle damage were also assessed. Ten healthy men volunteers performed 50 maximal eccentric muscle actions using the quadriceps muscles and muscle biopsy samples were taken from the exercised muscles before and 6 h, 2, 5 and 16 days post-exercise. Muscle damage was documented by its clinical and biochemical markers post exercise, while it was characterized by systemic cytokine responses and specific functional adaptations.Analyses of muscle biopsy samples revealed a rapid and transient up-regulation of MGF mRNA expression, which was followed by a prolonged increase of IGF-1Ea and IGF-1Eb mRNA expression. Patterns similar to those for mRNA expression were detected for MGF and IGF-1Ea expression at the protein level. The action of synthetic MGF E peptide differed from that of mature IGF-1 since its proliferative effect on C2C12 myoblast-like cells was not blocked by an anti-IGF-1 receptor neutralizing antibody and, in contrast to mature IGF-1, it activated only ERK1/2 and not Akt phosphorylation. It was concluded that the differential expression profile of IGF-1 isoforms in vivo and the the possible IGF-1R -independent MGF E peptide signalling in skeletal muscle-like cells support the notion of a specific and autonomous function of MGF on skeletal muscle regeneration.