Effects of Co-Transfection with Myostatin-Targeting siRNA and ActRIIB-Fc Fusion Protein on Skeletal Muscle Growth

• Material Type: 博士論文
• ISSN: 2189-6682
• Title: Effects of Co-Transfection with Myostatin-Targeting siRNA and ActRIIB-Fc Fusion Protein on Skeletal Muscle Growth
• Volume: 30 1
• Author/Editor: Bayarsaikhan, Od; Kawai, Nobuhiko; Mori, Hiroyo; Kinouchi, Nao; Nikawa, Takeshi; Tanaka, Eiji
• Author Heading: Bayarsaikhan, Od; Kawai, Nobuhiko; Mori, Hiroyo; Kinouchi, Nao; Nikawa, Takeshi; Tanaka, Eiji
• Publication, Distribution, etc.: 四国歯学会
• Publication Date: 2017-06-30
• Publication Date (W3CDTF): 2017-06-30
• Alternative Title: Myostatin-siRNAおよびActivinIIB型受容体融合タンパク質の共導入による骨格筋形成制御効果の検討
• Periodical title: Journal of Oral Health and Biosciences
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-23
• Date Granted (W3CDTF): 2017-03-23
• Dissertation Number: 甲第3085号
• Degree Type: 博士（歯学）
• Conferring No. (Dissertation): 甲第3085号
• Text Language Code: eng
• Subject Heading: myostatin; small-interfering RNAs; activin type IIB receptor; muscle hypertrophy
• Target Audience: 一般
• Note (General): Background: Myostatin (Mstn) is a secreted TGF-β family member that controls skeletal muscle growth, 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 combinative effects of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc on murine myoblast in vitro and in vivo. Materials and Methods: C2C12 cells were treated by Mstn-siRNA with or without ActRIIB-Fc at 0 and 48 h after differentiation. Myotube size was measured, and gene expression of Mstn, MuRF-1, MyoD and myogenin were analyzed. Furthermore, 11-week-old, male C57BL/6 mice were injected with atelocollagen (ATCOL)-mediated Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc locally into the masseter muscle twice a week. Histological and biochemical analyses were performed using the dissected muscles.Results: Transfection of Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc resulted in significant increases in the myotube diameter of the C2C12 cells compared with untreated control. Also, treatment with Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc could lead to an upregulation of MyoD and myogenin gene expression and downregulation of Mstn and MuRF-1. In vivo, muscle fibril hypertrophy was observed in both Mstn-siRNA and Mstn-siRNA/ActRIIB-Fc treated groups. Moreover, western blotting analysis showed that the p-Smad2/3 expression level was decreased by treatment of Mstn-siRNA/ActRIIB-Fc. In contrast, MyoD and myogenin protein levels were increased by combined treatment, compared with the other groups.Conclusions: These suggest that double inhibition of myostain is potentially useful for myogenesis and muscle growth promotion. This may be a good as new treatment remedy for patients with various muscle atrophies, including muscular dystrophy.
• DOI: info:doi/10.20738/johb.30.1_1; https://doi.org/info:doi/10.20738/johb.30.1_1
• Persistent ID (NDL): info:ndljp/pid/10993572; https://dl.ndl.go.jp/pid/10993572
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-12-04T02:02:48+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): https://repo.lib.tokushima-u.ac.jp/111062
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp