miR-29b contributes to multiple types of muscle atrophy.
miR-29b contributes to multiple types of muscle atrophy.
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miR-29b 导致多种类型的肌肉萎缩
DOI：
10.1038/ncomms15201
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发表时间：
2017-05-25
影响因子：
16.6
通讯作者：
Xiao J
中科院分区：
文献类型：
--
作者：
Li J;Chan MC;Yu Y;Bei Y;Chen P;Zhou Q;Cheng L;Chen L;Ziegler O;Rowe GC;Das S;Xiao J
许多microRNAs(miRNAs，miRs)已被证明在骨骼肌萎缩中发挥作用，但它们的作用尚不完全清楚。在这里，我们展示了miR-29b在细胞和小鼠模型中促进骨骼肌萎缩对不同萎缩刺激的反应。MiR-29b促进C2C12或原代成肌细胞分化为肌管的萎缩，相反，其抑制作用可减轻地塞米松、肿瘤坏死因子-α和过氧化氢诱导的萎缩。MiR-29b靶向胰岛素样生长因子-1和磷脂酰肌醇I3K(P85α)是诱导肌肉萎缩所必需的。在体内，miR-29b的过表达足以促进肌肉萎缩，而抑制miR-29b则可减轻失神经和制动所致的萎缩。这些数据提示miR-29b通过靶向胰岛素样生长因子-1和PI3K(p85α)参与多种类型的肌肉萎缩，抑制miR-29b可能是一种治疗不同刺激引起的肌肉萎缩的方法。骨骼肌萎缩可以发生在对不活动、禁食和衰老等刺激的反应中。在这里，作者表明，microRNA-29b的表达通过靶向IGF-1和PI3K来促进肌肉萎缩，并且它的抑制可以减轻由失神经和制动引起的小鼠肌肉萎缩。
A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli. Skeletal muscle atrophy can occur in response to stimuli such as inactivity, fasting, and ageing. Here the authors show that expression of microRNA-29b promotes muscle atrophy by targeting IGF-1 and PI3K, and that its inhibition attenuates atrophy induced by denervation and immobilization in mice.