【摘要】 背景:近年来,骨骼肌损伤的发生率越来越高,但骨骼肌本身的修复能力有限,研究骨骼肌损伤修复的分子机制对于骨骼肌损伤的治疗具有积极的作用。目的:探讨microRNA在骨骼肌再生中的作用。方法:Flexcell-5000拉伸装置周期性体外拉伸C2C12成肌细胞,选取合适的拉伸频率促进成肌发生;高通量测序检测对照组和拉伸组C2C12细胞中差异microRNA的表达;并对这些差异microRNA进行生物信息学分析。结果与结论:(1)10%形变、0.125 Hz拉伸频率可促进C2C12成肌细胞增殖,并可提高C2C12细胞中成肌因子Myo D和Myogenin的表达;(2)0.125 Hz拉伸组和对照组比较共有10个差异microRNA,包括上调的miR-340-5p/449c-5p/1941-3p和下调的miR-500-3p/1934-5p/31-3p/378a-5p/3473b/331-3p/5097;(3)这些microRNA可能通过多种的调节机制对C2C12成肌细胞的成肌过程进行调节,其中较为重要的通路有MAPK信号通路;(4)结果表明,低频率周期性力学刺激可能通过microRNA的变化引起成肌因子的表达升高最终引起成肌发生,其中可能参与的信号通路是MAPK信号通路。更多还原

【Abstract】 BACKGROUND: In recent years, the incidence of skeletal muscle injury becomes higher and higher, but the skeletal muscle repair ability is limited; therefore, studies on the molecular mechanism of skeletal muscle repair play a positive role in the treatment of skeletal muscle injury. OBJECTIVE: To explore the role of micro RNA in skeletal muscle regeneration. METHODS: C2C12 myoblasts were cyclic stretched in vitro by the Flexercell-5000 flexible device, and the appropriate stretch condition which could induce myogenesis was selected. The micro RNA expression alteration during mechanical stretch-induced myoblast myogenesis was explored using high-throughout sequencing, and the differentially expressed microRNAs were further studied by the bioinformatics analysis. RESULTS AND CONCLUSION: 10% deformation, 0.125 Hz cyclic mechanical stretch could promote myoblast proliferation and increase MyoD and Myogenin expressions in C2C12 myoblasts. Micro RNA expression profile alteration, including the downregulated miR-500-3 p/1934-5 p/31-3 p/378 a-5 p/3473 b/331-3 p/5097 and upregulated miR-340-5 p/449 c-5 p/1941-3 p, were all involved in the stretch-mediated myoblast myogenesis, and the MAPK signal pathway seemed to participate in this process. These results suggest that the low frequency of the cyclic mechanical stretch can upregulate the expression levels of myogenic regulatory factors through the alteration of Micro RNA expression, further inducing myogenesis, which the MAPK signal pathway may be involved in.更多还原