miR-378 attenuates muscle regeneration by delaying satellite cell activation and differentiation in mice.

miR-378 attenuates muscle regeneration by delaying satellite cell activation and differentiation in mice.
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DOI:
10.1093/abbs/gmw077
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发表时间:
2016-09
影响因子:
3.7
通讯作者:
P. Zeng;W. Han;Changyin Li;Hu Li;Dahai Zhu;Yong Zhang;Xiaohong Liu
P. Zeng;W. Han;Changyin Li;Hu Li;Dahai Zhu;Yong Zhang;Xiaohong Liu
中科院分区:
生物学3区
文献类型:
--
作者:
P. Zeng;W. Han;Changyin Li;Hu Li;Dahai Zhu;Yong Zhang;Xiaohong Liu

文献摘要

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出生后肌肉发育和再生过程中的骨骼肌质量和稳态很大程度上取决于成体肌肉干细胞(卫星细胞)。我们最近发现,miR-378 的整体过度表达显着减少了小鼠的骨骼肌质量。在当前的研究中,我们使用 miR-378 转基因(Tg)小鼠来评估 miR-378 对骨骼肌生长和再生的体内功能影响。骨骼肌组织的横断面分析表明,miR-378 Tg 小鼠的肌纤维数量和大小显着低于野生型小鼠。 miR-378 Tg 小鼠中心脏毒素诱导的肌肉再生减弱与卫星细胞活化和分化延迟有关。从机制上讲,miR-378被发现在体外和体内直接靶向肌肉细胞中的Igf1r。这些miR-378 Tg小鼠可能为研究骨骼肌在人类肌肉相关疾病(特别是肌少症)中的生理和病理作用提供模型。
Skeletal muscle mass and homeostasis during postnatal muscle development and regeneration largely depend on adult muscle stem cells (satellite cells). We recently showed that global overexpression of miR-378 significantly reduced skeletal muscle mass in mice. In the current study, we used miR-378 transgenic (Tg) mice to assess the in vivo functional effects of miR-378 on skeletal muscle growth and regeneration. Cross-sectional analysis of skeletal muscle tissues showed that the number and size of myofibers were significantly lower in miR-378 Tg mice than in wild-type mice. Attenuated cardiotoxin-induced muscle regeneration in miR-378 Tg mice was found to be associated with delayed satellite cell activation and differentiation. Mechanistically, miR-378 was found to directly target Igf1r in muscle cells both in vitro and in vivo These miR-378 Tg mice may provide a model for investigating the physiological and pathological roles of skeletal muscle in muscle-associated diseases in humans, particularly in sarcopenia.