State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China.
J Cell Physiol. 2015 Apr;230(4):752-7. doi: 10.1002/jcp.24838.
The pregnane X receptor (PXR, NR1I2) is a ligand-activated nuclear receptor which plays an essential role in organism's metabolic detoxification system by sensing the presence of xenobiotics and triggering detoxification responses. In addition to its role in xenobiotic metabolism, PXR has pleiotropic functions in regulating immune/inflammatory responses, cell proliferation, bile acid/cholesterol metabolism, glucose and lipid metabolism, steroid/endocrine homeostasis, and bone metabolism. Recent research suggests that the PXR is required for maintaining healthy commensalism between microbiota and gut. Interestingly, the metabolites such as indole derivatives from commensal microbes serve as the ligands for the PXR in intestinal epithelium forming an intricate mutualistic interaction between host and microbiota. PXR-regulated gene responses are controlled at epigenetic level by chromatin modifications, DNA methylation and noncoding RNA. Developmental alterations of the epigenome by exposure to the xenobiotics or diseases may produce persistent changes in PXR-regulated physiological responses. These new areas of research promise to vastly increase our understanding of PXR-regulated responses. In this review we highlight recent results on the epigenetic mechanisms for the PXR-regulated gene expression and discuss the physiological significance of these findings.
妊娠相关 X 受体 (PXR，NR1I2) 是一种配体激活的核受体，通过感知外源性物质的存在并触发解毒反应，在机体代谢解毒系统中发挥重要作用。除了在异生物质代谢中的作用外，PXR 在调节免疫/炎症反应、细胞增殖、胆汁酸/胆固醇代谢、糖和脂质代谢、甾体/内分泌稳态和骨代谢方面具有多种功能。最近的研究表明，PXR 对于维持微生物群和肠道之间的健康共生关系是必需的。有趣的是，来自共生微生物的代谢物（如吲哚衍生物）作为 PXR 在肠道上皮细胞中的配体，形成了宿主和微生物群之间复杂的共生相互作用。PXR 调节的基因反应在表观遗传水平上受到染色质修饰、DNA 甲基化和非编码 RNA 的控制。暴露于外源性物质或疾病导致的表观基因组发育改变可能会导致 PXR 调节的生理反应产生持久变化。这些新的研究领域有望极大地提高我们对 PXR 调节反应的理解。在这篇综述中，我们强调了最近关于 PXR 调节基因表达的表观遗传机制的研究结果，并讨论了这些发现的生理意义。
