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. Author manuscript; available in PMC: 2016 May 1.
Published in final edited form as: Drug Discov Today. 2014 Nov 20;20(5):618–628. doi: 10.1016/j.drudis.2014.11.011

Figure 2.

Figure 2

Major human diseases involving constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Various proteins can regulate CAR and PXR-mediated signaling pathways and thereby contribute to human diseases. PXR and CAR also regulate drug metabolism. CAR and PXR activation has been shown to be modulated by inflammation. (a) The presence of inflammatory mediators such as interleukin (IL)-6 significantly reduces the expression of PXR and CAR and their target genes [38,57]. IL-6 contributes to inflammatory disease. (b) CAR and PXR activation can downregulate gluconeogenesis-associated genes via crosstalk between CAR, PXR and the transcription factor forkhead box protein O1 (FOXO1), as proposed by Kodama et al. [40]. FOXO1 is suppressed in the presence of insulin. FOXO1 is a co-activator of CAR and PXR. Inversely, CAR and PXR can repress FOXO1 activity, reducing the expression of FOXO1-mediated downstream targets providing further insight into the role of CAR in regulating metabolic diseases [40]. Arrows indicate activation, stop bars indicate suppression.