Institute of Molecular Medicine, University of Texas John P and Katherine G McGovern Medical School, Houston, United States.
Int J Sports Med. 2023 Jul;44(9):609-617. doi: 10.1055/a-2035-8192. Epub 2023 Feb 14.
Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors, and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On the other hand, conditions such as diabetes and muscular dystrophy suppress expression of ERRs in the skeletal muscle, likely contributing to disease progression. We highlight key functions of ERRs in the skeletal muscle including the regulation of fiber type, mitochondrial metabolism, vascularization, and regeneration. We also describe how ERRs are regulated in the skeletal muscle, and their interaction with important muscle regulators (e. g. AMPK and PGCs). Finally, we identify critical gaps in our understanding of ERR signaling in the skeletal muscle, and suggest future areas of investigation to advance ERRs as potential targets for function promoting therapeutics in muscle diseases.
骨骼肌是一种高度可塑的组织，它可以通过运动和其他条件改变其代谢和收缩特性以及再生潜力。在骨骼肌可塑性的调节中，已经研究了多种信号因子，包括代谢物、激酶、受体和转录因子。最近，雌激素相关受体（ERRs）作为控制骨骼肌稳态的关键转录枢纽而出现。肌肉中高度表达的两种 ERR 亚型 ERRα 和 ERRγ 对各种细胞外信号（如运动、缺氧、禁食和饮食因素）做出反应，进而调节骨骼肌中的基因表达。另一方面，糖尿病和肌肉营养不良等疾病会抑制骨骼肌中 ERRs 的表达，这可能导致疾病进展。我们强调了 ERRs 在骨骼肌中的关键功能，包括调节纤维类型、线粒体代谢、血管生成和再生。我们还描述了 ERRs 在骨骼肌中的调节方式，以及它们与重要的肌肉调节剂（如 AMPK 和 PGCs）的相互作用。最后，我们确定了我们对 ERR 信号在骨骼肌中的理解中的关键差距，并提出了未来的研究领域，以推进 ERRs 作为肌肉疾病功能促进治疗的潜在靶点。
