Screening of Industrial and Agricultural Chemicals for Searching a Mouse PXR Activator Using Cell-Based Reporter Gene Assays

Nuclear receptors (NRs), a superfamily of ligand-activated transcription factors, are critical in cell growth, proliferation, differentiation, metabolism, and numerous biological events. NRs have been reported to play important roles in hepatomegaly (liver enlargement) and liver regeneration by regulating target genes or interacting with other signals. In this review, the roles and involved molecular mechanisms of NRs in hepatomegaly and liver regeneration are summarized and the future perspectives of NRs in the treatment of liver diseases are discussed.

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Nuclear Receptor-Mediated Hepatomegaly and Liver Regeneration: An Update

Zhao

Fan

Gao

et al. 2022

Drug Metab Dispos

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Role of Nuclear Receptors PXR and CAR in Xenobiotic-Induced Hepatocyte Proliferation and Chemical Carcinogenesis

Yoshinari

2019

Biological & Pharmaceutical Bulletin

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Nuclear receptors pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR) are xenobiotic-responsible transcriptional factors that belong to the same subfamily and are expressed abundantly in the liver. They play crucial roles in various liver functions including xenobiotic disposition and energy metabolism. CAR is also involved in xenobiotic-induced hepatocyte proliferation and hepatocarcinogenesis in rodents. However, there are some open questions on the association between chemical carcinogenesis and these nuclear receptors. These include the molecular mechanism for CAR-mediated hepatocyte proliferation and hepatocarcinogenesis. Another important question is whether PXR is associated with hepatocyte proliferation. We have recently reported a novel and unique function of PXR associated with murine hepatocyte proliferation: PXR activation alone does not induce hepatocyte proliferation but accelerates hepatocyte proliferation induced by various types of stimuli including CAR-or peroxisome proliferator-activated receptor alpha activating compounds, liver injury, and growth factors. We have also reported a role of yes-associated protein (YAP), a transcriptional cofactor controlling organ size and cell growth under the Hippo pathway, in CAR-mediated hepatocyte proliferation in mice. In this review, I will introduce our recent results as well as related studies on the roles of PXR and CAR in xenobiotic-induced hepatocyte proliferation and their molecular mechanisms.

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Screening of Industrial and Agricultural Chemicals for Searching a Mouse PXR Activator Using Cell-Based Reporter Gene Assays

Cited by 2 publications

References 20 publications

Nuclear Receptor-Mediated Hepatomegaly and Liver Regeneration: An Update

Nuclear Receptor-Mediated Hepatomegaly and Liver Regeneration: An Update

Role of Nuclear Receptors PXR and CAR in Xenobiotic-Induced Hepatocyte Proliferation and Chemical Carcinogenesis

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