【摘 要】
：
最新研究发现,内源性代谢中间产物在不同的生物学过程中都发挥着十分重要的调控功能,但目前已知具有这样功能的内源性代谢小分子却寥寥无几.我们通过系统发现鉴定了一个与骨骼肌发育相关的内源性代谢小分子X.实验表明内源性代谢小分子X剂量和时间依赖的促进C2C12和原代骨骼肌干细胞的增殖.同时,X可以协同IGF-1对肌细胞增殖的促进作用和拮抗Myostatin对骨骼肌干细胞增殖的抑制作用.同时,利用cardi
【机 构】
：
中国医学科学院基础医学研究所,医学分子生物学国家重点实验室,北京协和医学院基础学院,生物化学与分子生物学系,北京,100005
论文部分内容阅读
最新研究发现,内源性代谢中间产物在不同的生物学过程中都发挥着十分重要的调控功能,但目前已知具有这样功能的内源性代谢小分子却寥寥无几.我们通过系统发现鉴定了一个与骨骼肌发育相关的内源性代谢小分子X.实验表明内源性代谢小分子X剂量和时间依赖的促进C2C12和原代骨骼肌干细胞的增殖.同时,X可以协同IGF-1对肌细胞增殖的促进作用和拮抗Myostatin对骨骼肌干细胞增殖的抑制作用.同时,利用cardiotoxin诱导的小鼠骨骼肌再生模型,我们探讨了该小分子在骨骼肌再生种的功能.我们的结果表明,该内源性代谢小分子可以通过调控骨骼肌干细胞的激活和增值加速骨骼肌的再生.本研究的重要发现是,内源性代谢小分子X通过非Ras和不依赖能量代谢的方式激活Mek/Erk/Cyclin D1信号通路从而促进骨骼肌干细胞的激活、增殖和再生.结论：内源性代谢小分子X除了可以为细胞提供能量外,本研究首次证明了该代谢小分子还具有细胞信号分子的重要调控功能. 该研究结果为揭示内源性代谢中间产物的细胞信号转导功能提供了全新的视野和研究方向.同时,也为应用该代谢小分子治疗骨骼肌疾病展示了良好的临床前景.
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