Study on molecular regulation of muscle regeneration by mesenchymal cells

间充质细胞对肌肉再生的分子调控研究

• 批准号: 20590418
• 负责人: SUZUKI Yuko
• 金额: $ 3万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590418/
• 关键词: 骨格筋; 筋再生; 筋ジストロフィー; 細胞移植; 幹細胞; 筋芽細胞; Side Population細胞; CD248; 細胞老化; 筋衛星細胞; SP細胞; 骨格筋間葉系細胞

We found that CD31(-) CD45(-) side population (SP) cells in skeletal muscle are activated during muscle regeneration and promote the proliferation and the migration of grafted myoblasts. To further clarify the roles for CD31(-) CD45(-) SP cells, we generated CD248-sDTR-EGFP transgenic mice. However, the mice did not express sDTR-EGFP. This could be because the 1.0 kb upstream sequences of the CD248 gene were not enough to drive the expression of the reporter gene. We next analyzed the genome-wide gene expression pattern of mesenchymal cells (a descendent of CD31(-) CD45(-) SP cells) from dystrophin-deficient mice of different age. We found that mesenchymal cells in mdx mice experience cell senescence and immune response- and defense-related genes. These findings suggest that impaired muscle regeneration seen in advanced dystrophic muscle can be partly explained by exhausted mesenchymal cells, which otherwise promote muscle regeneration.

我们发现，骨骼肌中的CD 31（-）CD 45（-）侧群（SP）细胞在肌肉再生过程中被激活，并促进移植成肌细胞的增殖和迁移。为了进一步阐明CD 31（-）CD 45（-）SP细胞的作用，我们产生了CD 248-sDTR-EGFP转基因小鼠。然而，小鼠不表达sDTR-EGFP。这可能是因为CD 248基因的1.0 kb上游序列不足以驱动报告基因的表达。接下来，我们分析了来自不同年龄的肌营养不良蛋白缺陷小鼠的间充质细胞（CD 31（-）CD 45（-）SP细胞的后代）的全基因组基因表达模式。我们发现mdx小鼠的间充质细胞经历了细胞衰老和免疫反应及防御相关基因。这些发现表明，在晚期营养不良肌肉中看到的受损的肌肉再生可以部分解释为耗尽的间充质细胞，否则会促进肌肉再生。

项目成果

Muscle CD31(-) CD45(-) side population cells promote muscle regeneration by stimulating proliferation and migration of myoblasts

• DOI: 10.2353/ajpath.2008.070902
• 发表时间: 2008-09-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Motohashi, Norio;Uezumi, Akiyoshi;Takeda, Shin'ichi
• 通讯作者: Takeda, Shin'ichi

Recombinant Adeno-associated Virus Type 8-Mediated Extensive Therapeutic Gene Delivery into Skeletal Muscle of alpha-Sarcoglycan-Deficient Mice

重组腺相关病毒 8 型介导的广泛治疗性基因递送至 α-肌聚糖缺陷小鼠的骨骼肌

• 发表时间: 2008
• 期刊: Human Gene Therapy 19
• 作者: Nishiyama A;et al.
• 通讯作者: et al.

Post-translational Maturation of Dystroglycan Is Necessary for Pikachurin Binding and Ribbon Synaptic Localization

• DOI: 10.1074/jbc.m110.116343
• 发表时间: 2010-10-08
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kanagawa, Motoi;Omori, Yoshihiro;Toda, Tatsushi
• 通讯作者: Toda, Tatsushi

Downstream utrophin enhancer is required for expression of utrophin in skeletal muscle.

骨骼肌中肌营养蛋白的表达需要下游肌营养蛋白增强剂。

• 发表时间: 2008
• 期刊: Journal of Gene Medicine 10
• 作者: Tanihata J;Suzuki N;Miyagoe-Suzuki Y;Imaizumi K;Takeda S.
• 通讯作者: Takeda S.

Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro

原代 POMGnT1 缺失成肌细胞的体外增殖活性降低

• 发表时间: 2009
• 期刊: Mechanisms of Development 126
• 作者: Miyagoe-Suzuki Y;et al.
• 通讯作者: et al.