Prenatal myonuclei play a crucial role for skeletal muscle hypertrophy in rodents.

Prenatal myonuclei play a crucial role for skeletal muscle hypertrophy in rodents.
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产前肌核在啮齿类动物骨骼肌肥大中起着至关重要的作用。

DOI:
10.1152/ajpcell.00151.2016
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发表时间:
2017
期刊:
American Journal of Physiology Cell Physiology
影响因子:
--
通讯作者:
Nakai N
Nakai N
中科院分区:
--
文献类型:
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作者:
Kawano F;Ono Y;Fujita R;Watanabe A;Masuzawa R;Shibata K;Hasegawa S;Nakata K;Nakai N

文献摘要

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多核肌纤维是在胚胎和胎儿肌肉发生过程中肌祖细胞融合形成的。然而,在成年动物的骨骼肌纤维中,产前结合的肌核所起的作用还知之甚少。我们使用肌肉特异性报告鼠证明,尽管注射心脏毒素会导致出生前肌核的丢失,但产前肌核仍保留在成年比目鱼肌中。肌腱切断增效剂超负荷不能诱导成年大鼠比目鱼肌肌纤维的代偿性肥大,而尾部悬吊卸载可引起纤维萎缩。肥大功能的丧失与Igf1r基因转录起始点的组蛋白乙酰化水平降低有关,而组蛋白乙酰化是对超负荷没有反应的基因之一。取自新生大鼠比目鱼肌幼年的细胞移植后,结合增强Igf1r基因的组蛋白乙酰化,这些参数都得到了改善。这些结果表明,胎儿期肌核的存在与组蛋白乙酰化状态密切相关,组蛋白乙酰化状态可以调节肌纤维对生理刺激的反应性。
Multinucleated muscle fibers are formed by the fusion of myogenic progenitor cells during embryonic and fetal myogenesis. However, the role of prenatally incorporated myonuclei in the skeletal muscle fibers of adult animals is poorly understood. We demonstrated, using muscle-specific reporter mice, that the prenatal myonuclei remained in the adult soleus muscle, although cardiotoxin injection caused the loss of prenatal myonuclei. Overloading by the tendon transection of synergists failed to induce compensatory hypertrophy in regenerated soleus muscle fibers of adult rats, whereas unloading by tail suspension normally induced the fiber atrophy. Loss of hypertrophying function correlated with the lowered histone acetylation at the transcription start site ofIgf1rgene, which was one of the genes that did not respond to the overloading. These parameters were improved by the transplantation of cells harvested from the juvenile soleus muscles of neonatal rats in association with enhanced histone acetylation ofIgf1rgene. These results indicated that the presence of prenatal myonuclei was closely related to the status of histone acetylation, which could regulate the responsiveness of muscle fibers to physiological stimuli.