Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism.
Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism.
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DOI：
10.1621/nrs.07003
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Jetten AM
中科院分区：
文献类型：
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作者：
Jetten AM
在过去的几年里，我们对类维生素A相关孤儿受体RORα、-β和-γ（NR 1F 1 -3）、其作用机制、生理功能及其在多种病理学中的潜在作用的了解迅速增加。ROR缺陷小鼠的表征和基因表达谱分析，特别是提供了很大的见解ROR在各种生理过程的调节中的关键功能。这些研究表明，RORα在小脑的发育中起着关键作用，RORα和RORβ都是视网膜中光感受器成熟所必需的，而RORγ对包括淋巴结在内的几种次级淋巴组织的发育至关重要。ROR还涉及各种代谢途径、能量稳态和胸腺生成的调节。最近的研究确定了RORγ在未定型的CD 4 + T辅助细胞向Th 17细胞的谱系特化中的关键作用。此外，ROR调节生物钟的几个组成部分的表达，并可能在整合生物钟和下游（代谢）基因表达的节律模式中发挥作用。对ROR靶基因的研究为了解ROR控制这些过程的机制提供了新的视角。此外，一些报告已经提供了ROR在几种病理学中的潜在作用的证据，包括骨质疏松症、几种自身免疫性疾病、哮喘、癌症和肥胖症，并提出了ROR可能作为化疗干预的潜在靶点的可能性。这一前景被最近的证据所加强，这些证据表明ROR可以作为配体依赖性转录因子发挥作用。
The last few years have witnessed a rapid increase in our knowledge of the retinoid-related orphan receptors RORα, -β, and -γ (NR1F1-3), their mechanism of action, physiological functions, and their potential role in several pathologies. The characterization of ROR-deficient mice and gene expression profiling in particular have provided great insights into the critical functions of RORs in the regulation of a variety of physiological processes. These studies revealed that RORα plays a critical role in the development of the cerebellum, that both RORα and RORβ are required for the maturation of photoreceptors in the retina, and that RORγ is essential for the development of several secondary lymphoid tissues, including lymph nodes. RORs have been further implicated in the regulation of various metabolic pathways, energy homeostasis, and thymopoiesis. Recent studies identified a critical role for RORγ in lineage specification of uncommitted CD4+ T helper cells into Th17 cells. In addition, RORs regulate the expression of several components of the circadian clock and may play a role in integrating the circadian clock and the rhythmic pattern of expression of downstream (metabolic) genes. Study of ROR target genes has provided insights into the mechanisms by which RORs control these processes. Moreover, several reports have presented evidence for a potential role of RORs in several pathologies, including osteoporosis, several autoimmune diseases, asthma, cancer, and obesity, and raised the possibility that RORs may serve as potential targets for chemotherapeutic intervention. This prospect was strengthened by recent evidence showing that RORs can function as ligand-dependent transcription factors.