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Drug Metab Rev. 2013 Aug;45(3):300-10. doi: 10.3109/03602532.2013.795585. Epub 2013 May 24.

PXR cross-talks with internal and external signals in physiological and pathophysiological responses.

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1
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-Ku, Sendai , Japan. kodama@m.tohoku.ac.jp

Abstract

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.

PMID:
23701014
DOI:
10.3109/03602532.2013.795585
[Indexed for MEDLINE]

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