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

Susumu Kodama, Masahiko Negishi

Research output: Contribution to journalReview article

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)300-310
Number of pages11
JournalDrug Metabolism Reviews
Volume45
Issue number3
DOIs
Publication statusPublished - Aug 1 2013
Externally publishedYes

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Keywords

  • Cellular signal
  • Gene regulation
  • Nuclear receptor
  • Pregnane X receptor
  • Xenobiotics

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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