昼夜节律变化对肌萎缩症的影响及负重对肌肉萎缩的时间依赖性预防作用。
Day-Night Oscillation of Atrogin1 and Timing-Dependent Preventive Effect of Weight-Bearing on Muscle Atrophy.
机构信息
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,; Organization for University Research Initiatives, Waseda University, Tokyo, Japan.
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
出版信息
EBioMedicine. 2018 Nov;37:499-508. doi: 10.1016/j.ebiom.2018.10.057. Epub 2018 Nov 1.
BACKGROUND
Atrogin1, which is one of the key genes for the promotion of muscle atrophy, exhibits day-night variation. However, its mechanism and the role of its day-night variation are largely unknown in a muscle atrophic context.
METHODS
The mice were induced a muscle atrophy by hindlimb-unloading (HU). To examine a role of circadian clock, Wild-type (WT) and Clock mutant mice were used. To test the effects of a neuronal effects, an unilateral ablation of sciatic nerve was performed in HU mice. To test a timing-dependent effects of weight-bearing, mice were released from HU for 4 h in a day at early or late active phase (W-EAP and W-LAP groups, respectively).
FINDINGS
We found that the day-night oscillation of Atrogin1 expression was not observed in Clock mutant mice or in the sciatic denervated muscle. In addition, the therapeutic effects of weight-bearing were dependent on its timing with a better effect in the early active phase.
INTERPRETATION
These findings suggest that the circadian clock controls the day-night oscillation of Atrogin1 expression and the therapeutic effects of weight-bearing are dependent on its timing. FUND: Council for Science, Technology, and Innovation, SIP, "Technologies for creating next-generation agriculture, forestry, and fisheries".
背景
肌萎缩关键促进基因之一的 Atrogin1 表现出昼夜变化。然而，其在肌肉萎缩背景下的机制及其昼夜变化的作用在很大程度上尚不清楚。
方法
通过后肢去负荷（HU）诱导小鼠发生肌肉萎缩。为了研究生物钟的作用，使用了野生型（WT）和 Clock 突变小鼠。为了测试神经元作用的影响，在 HU 小鼠中进行了单侧坐骨神经切断术。为了测试承重的时间依赖性影响，将小鼠在一天中的早期或晚期活动期（W-EAP 和 W-LAP 组）从 HU 中释放 4 小时。
发现
我们发现，Atrogin1 表达的昼夜振荡在 Clock 突变小鼠或坐骨神经切断的肌肉中均未观察到。此外，承重的治疗效果取决于其时间，在早期活动期效果更好。
解释
这些发现表明，生物钟控制 Atrogin1 表达的昼夜振荡，承重的治疗效果取决于其时间。
基金
科学、创新和技术委员会、SIP“创建下一代农业、林业和渔业技术”。
Zotero 插件