Networking Strategies and Emerging Roles of Pregnane & xenobiotic Receptor (PXR) in Normal and Pathological States

The Pregnane & Xenobiotic Receptor (PXR), a member of the nuclear receptor family of ligand-activated transcription factors, is an integral component of the body's defense mechanism against toxic xenobiotics and endobiotic metabolites. Due to highly promiscuous nature and broad ligand specificity, this 'xenosensor' has emerged as a master-regulator of xenobiotic metabolism and regulator of all phases of drug metabolism and clearance. It has also been implicated to play an important role in induction of drug-drug interactions. During the past few years, research has unveiled some novel and mostly unanticipated roles for PXR in inflammation, lipid homeostasis, bone homeostasis, vitamin D metabolism, energy homeostasis, endocrine-related functions and cancer. Recent evidences have revealed existence of PXR cross-talk with several other cellular signaling pathways that profoundly expand the horizon of this promiscuous xenosensor. These cross-talks between PXR and other signaling pathways may elucidate molecular mechanisms to explain the involvement of PXR in several hitherto unanticipated physiological functions. The present article summarizes some of the important cross-talks of PXR with other nuclear receptors and different signaling pathways to describe how these cross-talks integrate into novel biological functions. It is anticipated that better understanding towards the mechanisms of PXR cross-talk might divulge novel therapeutic approaches to combat various diseases.