直近一年間の累計
アクセス数 : ?
ダウンロード数 : ?
ID 111062
タイトル別表記
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
著者
バイヤルサイハナ, オド 徳島大学大学院口腔科学教育部(口腔科学専攻)
キーワード
myostatin
small-interfering RNAs
activin type IIB receptor
muscle hypertrophy
資料タイプ
学位論文
抄録
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.
掲載誌名
Journal of Oral Health and Biosciences
ISSN
21896682
出版者
四国歯学会
30
1
開始ページ
1
終了ページ
7
並び順
1
発行日
2017-06-30
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨:LID201704281013.pdf
審査要旨:LID201704281014.pdf
論文本文:k3085_fulltext.pdf
本論文は,著者Od BAYARSAIKHANの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3085号
学位記番号
甲口第428号
学位授与年月日
2017-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系
病院
医学系