Pregnane X Receptor (PXR)

Pregnane X Receptor (PXR), a member of the nuclear receptor (NR) superfamily, is a ligand-activated transcription factor that plays a crucial role in the metabolism of xenobiotics and endobiotics in mammals. PXR was first recognized as an exogenous substance receptor regulating metabolizing enzymes and transporters and functioning in detoxification and drug metabolism in the liver. However, further research revealed that PXR acts as an equally important endogenous substance receptor in the metabolism and homeostasis of endogenous substances. PXR is highly distributed in small intestine, liver, rectum, colon and bladder, while its expression in other organs and tissues is either moderate, low or undetectable. PXR can be activated by numerous chemical compounds. Activated PXR, through direct binding to the genomic regions or indirect crosstalk with other transcriptional factors, controls various genes involved in biotransformation, transport, inflammation, oxidative stress and etc.
As a master regulator of xenobiotic response PXR adjusts the expression of many drug metabolizing enzymes (DME), such as cytochrome P450, uridine diphosphate (UDP)-glucuronosyltransferases, sulfotransferases and carboxylesterases. PXR also regulates drug-efflux pumps multi-drug resistance gene 1 (MDR1), MDR2, ATP-binding cassette transporter C 2 (ABCC) and anion-transporting polypeptide 2 (OATP). PXR is participated in tumor cell proliferation and growth, apoptosis and metastasis as well as in liver regeneration and hepatic proliferation, indicating the important role of PXR in cancer^[1][2].