Regulation of skeletal muscles by RNA interference for Myostatin

肌肉生长抑制素 RNA 干扰对骨骼肌的调节

• 批准号: 21792079
• 负责人: KINOUCHI Nao
• 金额: $ 2.83万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21792079/
• 关键词: 歯科矯正学; アテロコラーゲン; RNAi; マイオスタチン; 骨格筋

In this study, we examined whether systemic administration of the myostatin-siRNA /ATCOL (Mst-siRNA / ATCOL) complex effectively silenced myostatin expression in caveolin-3-deficient mouse model of limb-girdle muscular dystrophy 1C(LGMDIC) mice. We observed the enlargement of a number of skeletal muscles, and more in mice treated with Mst-siRNA /ATCOL muscles than control. Moreover, the average myofibril size for Mst-siRNA / ATCOL-treated muscle was increased by approximately 1. 2-fold relative to control. We evaluated the contractile properties of Mst-siRNA / ATCOL-treated LGMDIC muscle. Hypertrophied Mst-siRNA-positive LGMDIC fibers seemed to improve contractile force generation. Notably, the level of contractile force was improved by approximately 60% in Mst-siRNA / ATCOL-treated wild type muscles relative to control. These results provide evidence that ATCOL-mediated systemic administration of siRNAs may be a powerful therapeutic tool for muscular atrophy.

在这项研究中，我们检查了肌肉生长抑制素-siRNA/ATCOL（Mst-siRNA / ATCOL）复合物的全身施用是否有效地沉默了肢带型肌营养不良症1C（LGMDIC）小鼠的小窝蛋白-3缺陷小鼠模型中的肌肉生长抑制素表达。我们观察到许多骨骼肌的增大，并且在用Mst-siRNA /ATCOL肌肉处理的小鼠中比对照组更多。此外，Mst-siRNA /ATCOL处理的肌肉的平均肌原纤维尺寸增加约1。2-相对于对照组折叠。我们评估了Mst-siRNA /ATCOL处理的LGMDIC肌肉的收缩特性。肥大的Mst-siRNA阳性LGMDIC纤维似乎改善了收缩力的产生。值得注意的是，相对于对照，在Mst-siRNA /ATCOL处理的野生型肌肉中收缩力的水平提高了约60%。这些结果提供了证据表明，ATCOL介导的siRNA的全身给药可能是肌肉萎缩的有力治疗工具。

项目成果

Atelocollagen-mediated systemic administration of myostatin-targeting siRNA improves muscular atrophy in caveolin-3-deficient mice

• DOI: 10.1111/j.1440-169x.2010.01221.x
• 发表时间: 2011-01-01
• 期刊: DEVELOPMENT GROWTH & DIFFERENTIATION
• 影响因子: 2.5
• 作者: Kawakami, Emi;Kinouchi, Nao;Noji, Sumihare
• 通讯作者: Noji, Sumihare

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Atelocollagen-mediated Systemic Administration of Myostatin siRNA Improves Muscular Dystrophy

去端肽胶原介导的肌肉生长抑制素 siRNA 全身给药可改善肌营养不良症

• 发表时间: 2010
• 作者: 清水真一;友田正彦;高妻洋成;井上和人;青木繁夫;桃木至朗;上野邦一;田代亜紀子;石崎武志;宇野朋子;大田省一;小野田恵;大山亜紀子;宇都光恵;遠藤俊子;河口てる子;N.KINOUCHI
• 通讯作者: N.KINOUCHI