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• W2343986412 endingPage "1217" @default.
• W2343986412 startingPage "1198" @default.
• W2343986412 abstract "The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are well-known xenobiotic-sensing nuclear receptors with overlapping functions. However, there lacks a quantitative characterization to distinguish between the PXR and CAR target genes and signaling pathways in the liver. The present study performed a transcriptomic comparison of the PXR- and CAR-targets using RNA-Seq in livers of adult wild-type mice that were treated with the prototypical PXR ligand PCN (200mg/kg, i.p. once daily for 4days in corn oil) or the prototypical CAR ligand TCPOBOP (3mg/kg, i.p., once daily for 4days in corn oil). At the given doses, TCPOBOP differentially regulated many more genes (2125) than PCN (212), and 147 of the same genes were differentially regulated by both chemicals. As expected, the top pathways differentially regulated by both PCN and TCPOBOP were involved in xenobiotic metabolism, and they also up-regulated genes involved in retinoid metabolism, but down-regulated genes involved in inflammation and iron homeostasis. Regarding unique pathways, PXR activation appeared to overlap with the aryl hydrocarbon receptor signaling, whereas CAR activation appeared to overlap with the farnesoid X receptor signaling, acute-phase response, and mitochondrial dysfunction. The mRNAs of differentially regulated drug-processing genes (DPGs) partitioned into three patterns, namely TCPOBOP-induced, PCN-induced, as well as TCPOBOP-suppressed gene clusters. The cumulative mRNAs of the differentially regulated DPGs, phase-I and -II enzymes, as well as efflux transporters were all up-regulated by both PCN and TCPOBOPOP, whereas the cumulative mRNAs of the uptake transporters were down-regulated only by TCPOBOP. The absolute mRNA abundance in control and receptor-activated conditions was examined in each DPG category to predict the contribution of specific DPG genes in the PXR/CAR-mediated pharmacokinetic responses. The preferable differential regulation by TCPOBOP in the entire hepatic transcriptome correlated with a marked change in the expression of many DNA and histone epigenetic modifiers. In conclusion, the present study has revealed known and novel, as well as common and unique targets of PXR and CAR in mouse liver following pharmacological activation using their prototypical ligands. Results from this study will further support the role of these receptors in regulating the homeostasis of xenobiotic and intermediary metabolism in the liver, and aid in distinguishing between PXR and CAR signaling at various physiological and pathophysiological conditions. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie." @default.
• W2343986412 created "2016-06-24" @default.
• W2343986412 creator A5076743166 @default.
• W2343986412 creator A5083842467 @default.
• W2343986412 date "2016-09-01" @default.
• W2343986412 modified "2023-10-02" @default.
• W2343986412 title "RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome" @default.
• W2343986412 cites W1160080785 @default.
• W2343986412 cites W1485938486 @default.
• W2343986412 cites W1502153727 @default.
• W2343986412 cites W1519058668 @default.
• W2343986412 cites W1549189588 @default.
• W2343986412 cites W1640072252 @default.
• W2343986412 cites W177734819 @default.
• W2343986412 cites W1849836964 @default.
• W2343986412 cites W1966064283 @default.
• W2343986412 cites W1970717904 @default.
• W2343986412 cites W1971227490 @default.
• W2343986412 cites W1974435871 @default.
• W2343986412 cites W1974496620 @default.
• W2343986412 cites W1975284467 @default.
• W2343986412 cites W1975718637 @default.
• W2343986412 cites W1975875250 @default.
• W2343986412 cites W1977621555 @default.
• W2343986412 cites W1977995427 @default.
• W2343986412 cites W1978148089 @default.
• W2343986412 cites W1978718362 @default.
• W2343986412 cites W1978727518 @default.
• W2343986412 cites W1982056201 @default.
• W2343986412 cites W1987853577 @default.
• W2343986412 cites W1991020267 @default.
• W2343986412 cites W1995121576 @default.
• W2343986412 cites W1995397347 @default.
• W2343986412 cites W1995502179 @default.
• W2343986412 cites W1997228575 @default.
• W2343986412 cites W1998276272 @default.
• W2343986412 cites W2005272351 @default.
• W2343986412 cites W2005786213 @default.
• W2343986412 cites W2006461182 @default.
• W2343986412 cites W2006709297 @default.
• W2343986412 cites W2008825225 @default.
• W2343986412 cites W2009437300 @default.
• W2343986412 cites W2010104174 @default.
• W2343986412 cites W2012225201 @default.
• W2343986412 cites W2015711200 @default.
• W2343986412 cites W2016590530 @default.
• W2343986412 cites W2018743546 @default.
• W2343986412 cites W2021444563 @default.
• W2343986412 cites W2021769707 @default.
• W2343986412 cites W2022599869 @default.
• W2343986412 cites W2025681009 @default.
• W2343986412 cites W2025769132 @default.
• W2343986412 cites W2026776435 @default.
• W2343986412 cites W2028890879 @default.
• W2343986412 cites W2032693719 @default.
• W2343986412 cites W2035000881 @default.
• W2343986412 cites W2036051665 @default.
• W2343986412 cites W2036410410 @default.
• W2343986412 cites W2037874673 @default.
• W2343986412 cites W2040669411 @default.
• W2343986412 cites W2040872150 @default.
• W2343986412 cites W2041575918 @default.
• W2343986412 cites W2042096437 @default.
• W2343986412 cites W2044271813 @default.
• W2343986412 cites W2045746050 @default.
• W2343986412 cites W2050207944 @default.
• W2343986412 cites W2051167161 @default.
• W2343986412 cites W2054971398 @default.
• W2343986412 cites W2055784254 @default.
• W2343986412 cites W2057078403 @default.
• W2343986412 cites W2058926103 @default.
• W2343986412 cites W2066849510 @default.
• W2343986412 cites W2073714219 @default.
• W2343986412 cites W2073878222 @default.
• W2343986412 cites W2074151754 @default.
• W2343986412 cites W2077657779 @default.
• W2343986412 cites W2078965697 @default.
• W2343986412 cites W2081091627 @default.
• W2343986412 cites W2081759654 @default.
• W2343986412 cites W2082129438 @default.
• W2343986412 cites W2083447583 @default.
• W2343986412 cites W2085252511 @default.
• W2343986412 cites W2085397620 @default.
• W2343986412 cites W2087577664 @default.
• W2343986412 cites W2087639097 @default.
• W2343986412 cites W2088292892 @default.
• W2343986412 cites W2088479985 @default.
• W2343986412 cites W2095591310 @default.
• W2343986412 cites W2097815862 @default.
• W2343986412 cites W2100100424 @default.
• W2343986412 cites W2102278945 @default.
• W2343986412 cites W2103020094 @default.
• W2343986412 cites W2107733280 @default.
• W2343986412 cites W2108234281 @default.
• W2343986412 cites W2108665729 @default.
• W2343986412 cites W2111104494 @default.
• W2343986412 cites W2113524447 @default.
• W2343986412 cites W2113841093 @default.

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