ABSTRACT
The objective of this report was to analyse a potential role for FGF6 in muscle resistance to mechanical stress. Normal or regenerating muscles of FGF6 (-/-) mice versus wild-type mice were submitted to different protocols of damaging eccentric contractions (eccentric electrostimulation and intermittent downhill exercise). Then muscular structural properties were analysed by histological and immunochemistry techniques to evaluate the post-injury muscle recovery; their muscle contractile parameters (maximal tetanic force, kinetics properties and fatigue resistance) were assessed. The absence of FGF6 causes (1) a fast-to-slow myofibre type switch in adult control and regenerating Tibialis anterior (TA) muscle; (2) muscle weakness in regenerating muscles in animals submitted to eccentric exercise protocols due to aberrant extensive necrotic zones. These observations point out a crucial and unexpected role for FGF6 in muscle integrity and muscle protection against mechanical stress.
Subject(s)
Fibroblast Growth Factor 6/physiology , Muscle Contraction/genetics , Muscle Strength/genetics , Physical Stimulation , Stress, Mechanical , Animals , Fibroblast Growth Factor 6/genetics , Genetic Predisposition to Disease , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Contraction/physiology , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/physiology , Muscle Strength/physiology , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiology , Muscular Diseases/genetics , Regeneration/genetics , Regeneration/physiologyABSTRACT
Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the analyses of Fgf6 (-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remained largely unclear. Recent reports support the concept that FGF6 has a dual function in muscle regeneration, stimulating myoblast proliferation/migration and muscle differentiation/hypertrophy in a dose-dependent manner. The alternative use of distinct signaling pathways recruiting either FGFR1 or FGFR4 might explain the dual role of FGF6 in myogenesis. A role for FGF6 in the maintenance of a reserve pool of progenitor cells in the skeletal muscle has been also strongly suggested. The aim of this review is to summarize our knowledge on the involvement of FGF6 in myogenesis.