Expression of MyoD and myogenin in dystrophic mice, mdx and dy, during regeneration

Expression of MyoD and myogenin in dystrophic mice, mdx and dy, during regeneration
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DOI:
10.1007/s004010051172
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发表时间:
2000-06-01
影响因子:
12.7
通讯作者:
Nonaka, I
Nonaka, I
中科院分区:
医学1区
文献类型:
--
作者:
Jin, Y;Murakami, N;Nonaka, I

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研究了两种肌生成调节因子MyoD和myogenin在营养不良小鼠再生肌肉中的表达,并与化学诱导的再生过程进行了比较。首先,在单次局部麻醉盐酸布比卡因后,免疫组织化学测定了这两种蛋白在不同时间点的分布,布比卡因引起肌坏死,然后再生。MyoD在注射后18 h出现可检测水平,48 h表达达到最高水平,这与卫星细胞被激活并开始增殖的阶段一致。肌原素在注射后24 h可检测到,在注射后72 h新形成的肌管出现时表达达到最高水平。这两个基因也在表现出营养不良病理特征但与不同表型相关的dy和mdx小鼠的营养不良肌肉中表达。在mdr小鼠中,这两个基因在活跃的再生过程中以相当高的水平表达,而在dy小鼠中,MyoD和myogenin的表达随着纤维化的进展而下降。然而,与mdx小鼠相比,MyoD在dy小鼠较大的成熟肌管中相对更强烈地表达,表明再生活性延长。在dy和mdx小鼠中,MyoD和myogenin的表达量不同,表明这两种动物具有不同的再生活性。我们的研究结果证实,MyoD和myogenin基因的表达在卫星细胞(成肌细胞)的增殖和早期再生纤维(肌管)的发育过程中是必要的,即使在营养不良的肌肉中也是如此。
Expression of two myogenic regulatory factors, MyoD and myogenin, was studied in regenerating muscles of dystrophic mice and compared to a chemically induced regeneration process. First, the distribution of the two proteins was determined immunohistochemically at various time points after single administrations of a local anaesthetic, bupivacaine hydrochloride, which causes myonecrosis followed by regeneration. Detectable levels of MyoD appeared at 18 h and the expression reached their maximum levels at 48 h after the injection, which coincide with the stage when satellite cells are activated and start to proliferate. Myogenin became detectable in 24 h and its expression reached its highest level at 72 h after injection when newly formed myotubes appeared. The two genes were also expressed in the dystrophic muscles from dy and mdx mice which exhibit dystrophic pathological features but are associated with different phenotypes. In mdr mice the two genes were expressed at reasonably high levels in parallel with the active regenerating process, whereas in dy mice MyoD and myogenin expressions decreased as fibrosis progressed. However, MyoD was relatively more strongly expressed in the larger mature myotubes of dy mice than in those of mdx mice, suggesting prolonged regenerative activity. In dy and mdx mice, MyoD and myogenin were expressed in different quantities, indicating that these animals have distinct regenerating activities. Our findings confirm that expression of both MyoD and myogenin genes is necessary in the regenerative process for the proliferation of satellite cells (myoblasts) and for the development of early regenerating fibers (myotubes) even in dystrophic muscles.