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ID 114288
Title Alternative
Myostatin-Targeting siRNA and ActRIIB-Fc Fusion Protein
Author
Bayarsaikhan, Od Tokushima University
Keywords
myostatin
small-interfering RNAs
activin type IIB receptor
muscle hypertrophy
Content Type
Journal Article
Description
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.
Journal Title
Journal of Nutritional Science and Vitaminology
ISSN
03014800
18817742
NCID
AA00703822
Publisher
The Vitamin Society of Japan|Japan Society of Nutrition and Food Science|Center for Academic Publications Japan
Volume
63
Issue
4
Start Page
244
End Page
248
Published Date
2017-10-04
Rights
© The Vitamin Society of Japan, Japan Society of Nutrition and Food Science
本文データは学協会の許諾に基づきCiNiiから複製したものである
https://ci.nii.ac.jp/naid/130007314434
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DOI (Published Version)
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language
eng
TextVersion
Publisher
departments
Oral Sciences
University Hospital
Medical Sciences