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Therapeutic effects of exon skipping and losartan on skeletal muscle of mdx mice

Authors

  • Eun-Joo Lee,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Ah-Young Kim,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Eun-Mi Lee,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Myeong-Mi Lee,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Chang-Woo Min,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Kyung-Ku Kang,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Jin-Kyu Park,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Meeyul Hwang,

    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Soon-Hak Kwon,

    1. Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
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  • Jacques P. Tremblay,

    1. Department of Neurosciences, CHUL research Center, Quebec City, Quebec, Canada
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  • Kyu-Shik Jeong

    Corresponding author
    1. College of Veterinary Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
    2. Stem Cell Therapeutic Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea
    • Correspondence: Kyu-Shik Jeong, DVM, PhD, College of Veterinary Medicine, Kyungpook National University, #1370 sankyuk dong, buk gu, Daegu 702-701, Korea. Email: jeongks@knu.ac.kr

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  • Disclosure: None declared. There is no competing interest.

Abstract

Various attempts have been made to find treatments for Duchenne muscular dystrophy (DMD) patients. Exon skipping is one of the promising technologies for DMD treatment by restoring dystropin protein, which is one of the muscle components. It is well known that losartan, an angiotensin II type1 receptor blocker, promotes muscle regeneration and differentiation by lowering the level of transforming growth factor–beta1 signaling. In this study, we illustrated the combined effects of exon skipping and losartan on skeletal muscle of mdx mice. We supplied mdx mice with losartan for 2 weeks before exon skipping treatment. The losartan with the exon skipping group showed less expression of myf5 than the losartan treated group. Also the losartan with exon skipping group recovered normal muscle architecture, in contrast to the losartan group which still showed many central nuclei. However, the exon skipping efficiency and the restoration of dystrophin protein were lower in the losartan with exon skipping group compared to the exon skipping group. We reveal that losartan promotes muscle regeneration and shortens the time taken to restore normal muscle structure when combined with exon skipping. However, combined treatment of exon skipping and losartan decreases the restoration of dystrophin protein meaning decrease of exon skipping efficiency.

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