Department of Physiology and Pathophysiology, Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.
The Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.
Int J Mol Sci. 2024 Oct 22;25(21):11340. doi: 10.3390/ijms252111340.
Retinoic-acid-related orphan receptors (RORs) are transcription factors belonging to the nuclear receptor subfamily consisting of RORα, RORβ, and RORγ. By binding to the ROR response elements (ROREs) on target gene promoters, RORs regulate a wide variety of cellular processes, including autophagy, mitophagy, oxidative stress, and inflammation. The regulatory roles of RORs are observed in cardiac cells, hepatocytes, pulmonary epithelial cells, renal cells, immune cells, and cancer cells. A growing body of clinical and experimental evidence suggests that ROR expression levels are markedly reduced under different pathological and stress conditions, suggesting that RORs may play a critical role in the pathogenesis of a variety of disease states, including myocardial infarction, immune disorders, cancer, and metabolic syndrome. Reductions in RORs are also associated with inhibition of autophagy, increased reactive oxygen species (ROS), and increased cell death, underscoring the importance of RORs in the regulation of these processes. Herein, we highlight the relationship between RORs and homeostatic processes that influence cell viability. Understanding how these intricate processes are governed at the cellular level is of high scientific and clinical importance to develop new therapeutic strategies that modulate ROR expression and disease progression.
维甲酸相关孤儿受体（RORs）是核受体亚家族的转录因子，包括 RORα、RORβ 和 RORγ。RORs 通过与靶基因启动子上的 ROR 反应元件（ROREs）结合，调节多种细胞过程，包括自噬、线粒体自噬、氧化应激和炎症。RORs 的调节作用在心肌细胞、肝细胞、肺上皮细胞、肾细胞、免疫细胞和癌细胞中都有观察到。越来越多的临床和实验证据表明，在不同的病理和应激条件下，ROR 的表达水平显著降低，这表明 ROR 可能在多种疾病状态的发病机制中发挥关键作用，包括心肌梗死、免疫紊乱、癌症和代谢综合征。ROR 的减少也与自噬抑制、活性氧（ROS）增加和细胞死亡增加有关，这强调了 ROR 在这些过程调节中的重要性。本文重点介绍了 ROR 与影响细胞活力的动态平衡过程之间的关系。了解这些复杂过程在细胞水平上是如何被调控的，对于开发调节 ROR 表达和疾病进展的新治疗策略具有重要的科学和临床意义。
