title: Impaired adaptive response to mechanical overloading in dystrophic skeletal muscle.
abstract: Dystrophin contributes to force transmission and has a protein-scaffolding role for a variety of signaling complexes in skeletal muscle. In the present study, we tested the hypothesis that the muscle adaptive response following mechanical overloading (ML) would be decreased in MDX dystrophic muscle lacking dystrophin. We found that the gains in muscle maximal force production and fatigue resistance in response to ML were both reduced in MDX mice as compared to healthy mice. MDX muscle also exhibited decreased cellular and molecular muscle remodeling (hypertrophy and promotion of slower/oxidative fiber type) in response to ML, and altered intracellular signalings involved in muscle growth and maintenance (mTOR, myostatin, follistatin, AMPKα1, REDD1, atrogin-1, Bnip3). Moreover, dystrophin rescue via exon skipping restored the adaptive response to ML. Therefore our results demonstrate that the adaptive response in response to ML is impaired in dystrophic MDX muscle, most likely because of the dystrophin crucial role.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, CNRS EAC4413, Unit of Functional and Adaptive Biology, Laboratory of Stress and Pathologies of the Cytoskeleton, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Joanne
authors.forename: Christophe
authors.initials: C
authors.lastname: Hourdé
authors.forename: Julien
authors.initials: J
authors.lastname: Ochala
authors.forename: Yvain
authors.initials: Y
authors.lastname: Caudéran
authors.forename: Fadia
authors.initials: F
authors.lastname: Medja
authors.forename: Alban
authors.initials: A
authors.lastname: Vignaud
authors.forename: Etienne
authors.initials: E
authors.lastname: Mouisel
authors.forename: Wahiba
authors.initials: W
authors.lastname: Hadj-Said
authors.forename: Ludovic
authors.initials: L
authors.lastname: Arandel
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia
authors.forename: Aurélie
authors.initials: A
authors.lastname: Goyenvalle
authors.forename: Rémi
authors.initials: R
authors.lastname: Mounier
authors.forename: Daria
authors.initials: D
authors.lastname: Zibroba
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamato
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.forename: Onnik
authors.initials: O
authors.lastname: Agbulut
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001696:Biomechanical Phenomena; D051379:Mice; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000502:physiology*; D020388:Muscular Dystrophy, Duchenne / Q000503:physiopathology; D015398:Signal Transduction