Telethonin与MSTN在进行性肌营养不良患者肌肉中的表达

Expression of Telethonin and MSTN in the progressive muscular dystrophy patients

目的Telethon in是一种重要的肌节蛋白,肌肉抑制素(myostatin,MSTN)是骨骼肌生长发育抑制因子,本文主要目的是探讨Telethon in和MSTN基因与进行性肌营养不良病理发生的相关性。方法采用W estern b lot方法分析肌营养不良患者中Telethon in和MSTN蛋白的表达水平;为进一步分析Telethon in蛋白对肌营养不良病理发生的作用,构建了Telethon in的反义表达载体,转染肌原性细胞系C2C12,研究阻断Telethon in基因表达(Knockdown)对成肌细胞增殖分化的影响。结果发现在一些肌营养不良患者中Telethon in蛋白表达缺失,而在这些患者的肌肉组织中MSTN蛋白表达正常但存在加工障碍;此结果提示,Telethon in蛋白可能参与MSTN蛋白的加工成熟过程。采用反义技术阻断Telethon in基因表达后,C2C12细胞增殖受到明显抑制。结论Telethon in和MSTN可能与一些类型肌营养不良的病理发生密切相关。

Objective To investigate possible was impact of telethonin and myostatin on the pathogenesis of progressive muscular dystrophy. Methods We analyzed the expressions of telethonin and myostatin in the progressive muscular dystrophy patients by Western Blot. In order to further investigate the function of telethonin implicated in the pathogenesis of muscular dystrophy, we used the myoblast cell line C2C12 to study the function of telethonin in vitro. The construct with antisense-telethonin was transfected into C2C12 to knockdown the telethonin expression in C2C12 cells. Results Telethonin protein was absent in the dystrophic muscles of five patients. Interestingly, the processing and maturation of myostatin protein were inhibited in the five telethonin-absent patients, which suggested that telethonin was likely involved in the maturation of myostatin. After telethonin knockdown by antisense-telethonin construct transfection, the proliferation of C2C12 was dramatically inhibited. Conclusion The interaction between telethonin and myostatin may have impact on the pathogenesis of some types of progressive muscular dystrophy.