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

Cyclosporin A Promotes in vivo Myogenic Response in Collagen VI-Deficient Myopathic Mice.

MOLON, SIBILLA;MORBIDONI, VALERIA;BRAGHETTA, PAOLA;BLAAUW, BERT;URCIUOLO, ANNA;BONALDO, PAOLO
2014

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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3042353
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