title: Cyclosporin A Promotes in vivo Myogenic Response in Collagen VI-Deficient Myopathic Mice.
abstract: Mutations of genes encoding for collagen VI cause various muscle diseases in humans, including Bethlem myopathy and Ullrich congenital muscular dystrophy. Collagen VI null (Col6a1 (-/-)) mice are affected by a myopathic phenotype with mitochondrial dysfunction, spontaneous apoptosis of muscle fibers, and defective autophagy. Moreover, Col6a1 (-/-) mice display impaired muscle regeneration and defective self-renewal of satellite cells after injury. Treatment with cyclosporin A (CsA) is effective in normalizing the mitochondrial, apoptotic, and autophagic defects of myofibers in Col6a1 (-/-) mice. A pilot clinical trial with CsA in Ullrich patients suggested that CsA may increase the number of regenerating myofibers. Here, we report the effects of CsA administration at 5 mg/kg body weight every 12 h in Col6a1 (-/-) mice on muscle regeneration under physiological conditions and after cardiotoxin (CdTx)-induced muscle injury. Our findings indicate that CsA influences satellite cell activity and triggers the formation of regenerating fibers in Col6a1 (-/-) mice. Data obtained on injured muscles show that under appropriate administration, regimens CsA is able to stimulate myogenesis in Col6a1 (-/-) mice by significantly increasing the number of myogenin (MyoG)-positive cells and of regenerating myofibers at the early stages of muscle regeneration. CsA is also able to ameliorate muscle regeneration of Col6a1 (-/-) mice subjected to multiple CdTx injuries, with a concurrent maintenance of the satellite cell pool. Our data show that CsA is beneficial for muscle regeneration in Col6a1 (-/-) mice.
authors.affiliation: Department of Molecular Medicine, University of Padova , Padova , Italy ; Interdepartmental Research Center E. Piaggio, University of Pisa , Pisa , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gattazzo
authors.affiliation: Department of Molecular Medicine, University of Padova , Padova , Italy.
authors.forename: Sibilla
authors.initials: S
authors.lastname: Molon
authors.affiliation: Department of Molecular Medicine, University of Padova , Padova , Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Morbidoni
authors.affiliation: Department of Molecular Medicine, University of Padova , Padova , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Braghetta
authors.affiliation: Department of Biomedical Sciences, University of Padova , Padova , Italy.
authors.forename: Bert
authors.initials: B
authors.lastname: Blaauw
authors.affiliation: Department of Molecular Medicine, University of Padova , Padova , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Urciuolo
authors.affiliation: Department of Molecular Medicine, University of Padova , Padova , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
keywords: animal model; collagen VI; congenital muscular dystrophy; cyclosporin A; muscle regeneration; skeletal muscle