Co-Administration of Myostatin-Targeting siRNA and ActRIIB-Fc Fusion Protein Increases Masseter Muscle Mass and Fiber Size
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- BAYARSAIKHAN Od
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School
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- KAWAI Nobuhiko
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School Department of Nutritional Physiology, Institute of Biomedical Sciences, Tokushima University Graduate School
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- MORI Hiroyo
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School
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- KINOUCHI Nao
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School
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- NIKAWA Takeshi
- Department of Nutritional Physiology, Institute of Biomedical Sciences, Tokushima University Graduate School
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- TANAKA Eiji
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School
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抄録
Myostatin, a member of the TGF-β superfamily, is a negative regulator of skeletal muscle cell growth and differentiation, and binds with high affinity to the activin type IIB receptor (ActRIIB). The soluble ligand-binding domain of ActRIIB fused to the Fc domain of IgG (ActRIIB-Fc) potently binds and inhibits TGF-β family members in muscle, leading to rapid and marked muscle growth. The present study was designed to assess the effectiveness of the co-delivery of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc into skeletal muscle as a potential treatment of atrophic myopathies. Eleven-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA with/without ActRIIB-Fc locally into the masseter muscle twice a week. Inhibition of myostatin function by the combination of Mstn-siRNA and ActRIIB-Fc increased muscle weight and myofibril size in murine masseter muscle. Real-time RT-PCR analysis revealed significant downregulation of myostatin mRNA expression in both the Mstn-siRNA-treated and the combination treatment group. Furthermore, myogenin mRNA expression was upregulated in the combination treatment group, while MuRF-1 and Atrogin-1 mRNA expression was downregulated compared to administration of each compound alone. These findings suggest that double inhibition of myostatin is a potentially useful treatment strategy to increase muscle mass and fiber size and could be a useful treatment of patients with various muscle atrophies, including muscular dystrophy.
収録刊行物
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- Journal of Nutritional Science and Vitaminology
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Journal of Nutritional Science and Vitaminology 63 (4), 244-248, 2017
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詳細情報 詳細情報について
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- CRID
- 1390282681300792320
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- NII論文ID
- 130007314434
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- NII書誌ID
- AA00703822
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- ISSN
- 18817742
- 03014800
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- NDL書誌ID
- 028470821
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- PubMed
- 28978871
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可