Arrdc2 and Arrdc3 elicit divergent changes in gene expression in skeletal muscle following anabolic and catabolic stimuli
Arrdc2 and Arrdc3 elicit divergent changes in gene expression in skeletal muscle following anabolic and catabolic stimuli
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DOI：
10.1152/physiolgenomics.00007.2019
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发表时间：
2019-06-01
影响因子：
4.6
通讯作者：
Eroshkin, Alexey M.
中科院分区：
文献类型：
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作者：
Gordon, Bradley S.;Rossetti, Michael L.;Eroshkin, Alexey M.
骨骼肌是一种高度可塑性的器官，调节体内的各种过程。因此，骨骼肌的损失是与许多病症相关的发病率和死亡率风险增加的基础。然而，没有疗法可用于对抗萎缩性疾病期间肌肉质量的损失，这部分是由于对合成代谢和分解代谢刺激改变的分子网络的不完全理解。因此，目前的目标是确定新的基因网络调制这样的刺激。为此，对来自禁食过夜或禁食过夜并在第二天早上再喂食的小鼠的胫骨前肌的总RNA进行微阵列分析。再喂养刺激改变了与信号转导相关的基因的表达。具体地，通过再喂养，含有α抑制蛋白结构域2（Arrdc 2）和含有α抑制蛋白结构域3（Arrdc 3）的表达显著降低70-85%。随后的分析表明，这些基因的表达也被机械过载降低了50-75%，营养素和机械过载的组合协同作用降低了Arrdc 2和Arrdc 3的表达。匡威，抑制生长的刺激，如睾酮耗竭或急性有氧运动增加了骨骼肌中Arrdc 2和Arrdc 3的表达。虽然Arrdc 2和Arrdc 3在合成代谢或分解代谢刺激后表现出不同的表达变化，但Arrdc基因家族的其他成员在分析的条件下没有表现出一致的表达变化。因此，Arrdc 2和Arrdc 3是一组新的基因，可能与骨骼肌质量的调节有关。
Skeletal muscle is a highly plastic organ regulating various processes in the body. As such, loss of skeletal muscle underlies the increased morbidity and mortality risk that is associated with numerous conditions. However, no therapies are available to combat the loss of muscle mass during atrophic conditions, which is due in part to the incomplete understanding of the molecular networks altered by anabolic and catabolic stimuli. Thus, the current objective was to identify novel gene networks modulated by such stimuli. For this, total RNA from the tibialis anterior muscle of mice that were fasted overnight or fasted overnight and refed the next morning was subjected to microarray analysis. The refeeding stimulus altered the expression of genes associated with signal transduction. Specifically, expression of alpha arrestin domain containing 2 (Arrdc2) and alpha arrestin domain containing 3 (Arrdc3) was significantly lowered 70-85% by refeeding. Subsequent analysis showed that expression of these genes was also lowered 50-75% by mechanical overload, with the combination of nutrients and mechanical overload acting synergistically to lower Arrdc2 and Arrdc3 expression. On the converse, stimuli that suppress growth such as testosterone depletion or acute aerobic exercise increased Arrdc2 and Arrdc3 expression in skeletal muscle. While Arrdc2 and Arrdc3 exhibited divergent changes in expression following anabolic or catabolic stimuli, no other member of the Arrdc family of genes exhibited the consistent change in expression across the analyzed conditions. Thus, Arrdc2 and Arrdc3 are a novel set of genes that may be implicated in the regulation of skeletal muscle mass.