Short- and Long-Term Hindlimb Immobilization and Reloading: Profile of Epigenetic Events in Gastrocnemius
Short- and Long-Term Hindlimb Immobilization and Reloading: Profile of Epigenetic Events in Gastrocnemius
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DOI：
10.1002/jcp.25635
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发表时间：
2017-06-01
影响因子：
5.6
通讯作者：
Barreiro, Esther
中科院分区：
文献类型：
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作者：
Chacon-Cabrera, Alba;Gea, Joaquim;Barreiro, Esther
骨骼肌功能障碍和萎缩是伴随慢性疾病的特征。表观遗传事件调节肌肉质量和功能维持。我们假设，暴露于后肢制动（I）和I后恢复的小鼠骨骼肌中，表观遗传事件（肌肉富集的microRNA和组蛋白乙酰化）和已知信号肌肉萎缩的转录因子乙酰化的模式可能在早期和晚期时间点之间存在差异。在暴露于周期性刺激的小鼠的腓肠肌中评估体重和肌肉重量、握力、肌肉富集的microRNA、组蛋白脱乙酰酶（HDAC）、蛋白质、组蛋白和转录因子（TF）的乙酰化、肌源性TF因子和肌肉表型。（1，2，3，7，15和30天，I组）后肢制动，并在那些暴露于重新加载不同的时间段（1、3、7、15和30天，R组）。与非固定对照组相比，I组小鼠的肌肉重量，肢体力量，microRNA，特别是miR-486，SIRT 1水平以及慢缩和快缩横截面积均降低，而Pax 7和乙酰化FoxO 1和FoxO 3水平升高。去除夹板后的肌肉重新加载通过增加microRNA，特别是miR- 486和SIRT 1含量，同时降低乙酰化FoxO 1和FoxO 3水平，改善了肌肉质量损失，力量和纤维萎缩。在这个废用性肌肉萎缩的小鼠模型中，肌肉富集的microRNA，特别是miR- 486，通过Pax 7调节延迟腓肠肌卸载后的肌细胞分化。FoxO 1和FoxO 3的乙酰化似乎会导致肌肉质量损失和萎缩，而通过SIRT 1使这些因子脱乙酰化将使肌肉纤维再生。(C)2016 Wiley Periodicals，Inc.
Skeletal muscle dysfunction and atrophy are characteristic features accompanying chronic conditions. Epigenetic events regulate muscle mass and function maintenance. We hypothesized that the pattern of epigenetic events (muscle-enriched microRNAs and histone acetylation) and acetylation of transcription factors known to signal muscle wasting may differ between early- and late-time points in skeletal muscles of mice exposed to hindlimb immobilization (I) and recovery following I. Body and muscle weights, grip strength, muscleenriched microRNAs, histone deacetylases (HDACs), acetylation of proteins, histones, and transcription factors (TF), myogenic TF factors, and muscle phenotype were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15, and 30 days, I groups) of hindlimb immobilization, and in those exposed to reloading for different periods of time (1, 3, 7, 15, and 30 days, R groups) following 7-day immobilization. Compared to non-immobilized controls, muscle weight, limb strength, microRNAs, especially miR-486, SIRT1 levels, and slow- and fast-twitch cross-sectional areas were decreased in mice of I groups, whereas Pax7 and acetylated FoxO1 and FoxO3 levels were increased. Muscle reloading following splint removal improved muscle mass loss, strength, and fiber atrophy, by increasing microRNAs, particularly miR- 486, and SIRT1 content, while decreasing acetylated FoxO1 and FoxO3 levels. In this mouse model of disuse muscle atrophy, muscle-enriched microRNAs, especially miR- 486, through Pax7 regulation delayed muscle cell differentiation following unloading of gastrocnemius muscle. Acetylation of FoxO1 and 3 seemed to drive muscle mass loss and atrophy, while deacetylation of these factors through SIRT1 would enable the muscle fibers to regenerate. (C) 2016 Wiley Periodicals, Inc.