Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-Ku, Sendai , Japan.
Drug Metab Rev. 2013 Aug;45(3):300-10. doi: 10.3109/03602532.2013.795585. Epub 2013 May 24.
Pregnane X receptor (PXR), an orphan member of the nuclear receptor superfamily, is a major xeno-sensing transcription factor. In response to xenobiotic exposure, PXR regulates genes involved in the metabolism and transport of xenobiotics to protect the body from their harmful effects. Recent progress has revealed that PXR responds not only to such external signals but also to internal signals to help the body adapt to changes in the internal environment, including dysregulation of the immune system. PXR responds to external and internal signals by up- or down-regulating certain metabolic pathways and cellular signals through gene regulation. PXR is a potential therapeutic target for inflammatory as well as metabolic diseases, although its activation may also have unfavorable effects on human health. This review will discuss the recent progress in the understanding of the physiological and pathophysiological roles of PXR and their implications in human diseases and drug therapy by elucidating the molecular mechanisms underlying PXR-mediated gene regulation.
妊娠相关 X 受体 (PXR)，核受体超家族的孤儿成员，是主要的外源性感知转录因子。在应对外源物暴露时，PXR 调节涉及外源物代谢和转运的基因，以保护身体免受其有害影响。最近的研究进展表明，PXR 不仅对外源信号做出反应，还对内源信号做出反应，以帮助身体适应内部环境的变化，包括免疫系统失调。PXR 通过基因调控上调或下调某些代谢途径和细胞信号来响应外部和内部信号。PXR 是炎症和代谢疾病的潜在治疗靶点，尽管其激活也可能对人类健康产生不利影响。本综述将通过阐明 PXR 介导的基因调控的分子机制，讨论对 PXR 的生理和病理生理作用及其在人类疾病和药物治疗中的意义的最新认识。
