Article Figures & Data
Figures
- Fig. 1.
The structure, function of NRs, and related liver diseases.
- Fig. 2.
Mechanisms involved in NR-mediated hepatomegaly (A) and liver regeneration (B).
- Fig. 3.
YAP signaling pathway mediates CAR-, PXR-, or PPARα-induced hepatomegaly and liver regeneration.
Tables
Target Agonist/Antagonist Drug/Compound Reference(s) PXR Agonist PCN Jiang et al., 2019 Rifampicin Jiang et al., 2019 Imazalil Shizu et al., 2018 Dexamethasone Jiao et al., 2020 Schisandrol B Zhao et al., 2021 Mifepristone Yao et al., 2021 Antagonist ET-743 Chai et al., 2020 Polychlorinated Biphenyls Mani et al., 2013 Biphenyls Mani et al., 2013 Fluconazole Mani et al., 2013 Enilconazole Mani et al., 2013 Sesamin Mani et al., 2013 Metformin Mani et al., 2013 PPARα Agonist Clofibrate Lenhard et al., 1999 WY-14643 Fan et al., 2022 Gemfibrozil Lenhard et al., 1999 Fenofibrate Willson et al., 2000 Antagonist GW6471 Stebbins et al., 2017 MK886 Stebbins et al., 2017 NXT629 Stebbins et al., 2017 PPARγ Agonist Rosiglitazone Turmelle et al., 2006 Pioglitazone Collino et al., 2010 Antagonist GW9662 Almahmoud et al., 2021 T0070907 Almahmoud et al., 2021 CAR Agonist CITCO Tschuor et al., 2016 Phenobarbital Huang et al., 2005 TCPOBOP Gao et al., 2021 Antagonist PK11195 Mackowiak et al., 2019 CINPA1 Mackowiak et al., 2019 LXR Agonist T0901317 Jung et al., 2011 GW3965 Minniti et al., 2020 Antagonist GSK2033 Helder et al., 2020 FXR Agonist WAY-362450 Wu et al., 2019 OCA de Haan et al., 2021 Antagonist DY268 Jiang et al., 2021 FLG249 Jiang et al., 2021 NRs Activators or Agonists Effects on liver size and Regeneration Reference(s) PXR PCN Induces liver enlargement and liver regeneration via activation of YAP signaling pathway Jiang et al., 2019 PXR Rifampicin Induces liver enlargement and liver regeneration via activation of YAP signaling pathway Jiang et al., 2019 PXR Imazalil Activates PXR to elevate hepatocyte proliferation induced by CAR Shizu et al., 2018 PXR Dexamethasone Induces hepatomegaly by the activation of YAP signaling pathway and lipid accumulation Jiao et al., 2020 PXR Schisandrol B Induces hepatomegaly and hepatocyte proliferation by activation of YAP signaling pathway Zhao et al., 2021 PXR Mifepristone Induces hepatomegaly by promoting PXR and YAP nuclear translocation Yao et al., 2021 PPARα Clofibrate Induces liver enlargement Lenhard et al., 1999 PPARα WY-14643 Promotes liver enlargement and liver regeneration via activation of YAP-TEAD signaling pathway Fan et al., 2022 PPARα Gemfibrozil Induces liver enlargement Lenhard et al., 1999 PPARγ Rosiglitazone Impairs liver regeneration process by down-regulation of cyclin expression Turmelle et al., 2006 CAR CITCO Promotes hepatomegaly and liver regeneration in SFSS model Tschuor et al., 2016 CAR Phenobarbital Induces hepatomegaly by activating Mdm2 gene expression Huang et al., 2005 CAR TCPOBOP Promotes hepatomegaly by activating YAP signaling pathway Abe et al., 2018; Gao et al., 2021 LXR T0901317 (LXRT) Induces hepatomegaly with an increased level of triglyceride Jung et al., 2011 FXR WAY-362450 Induces hepatomegaly by activating cyclin D1 Wu et al., 2019 NRs Effects Mechanisms Reference(s) PXR Hepatomegaly↑ Induces hyperplasia and hypertrophy by YAP signaling pathway Jiang et al., 2019 PXR Liver regeneration↑ Accelerates liver regeneration by YAP signaling pathway Yoshinari, 2019; Jiang et al., 2019 PPARα Hepatomegaly↑ 1. Induces gene expression of Ras, Rho α, and c-Myc oncogene expression, which are important for hepatocyte proliferation and hepatic hyperplasia; Morimura et al., 2006, Shah et al., 2007; Fan et al., 2022 2. Interacts with YAP-TEAD signaling pathway PPARα Liver regeneration↑ 1. Interacts with YAP-TEAD signaling pathway and induces liver regeneration Fan et al., 2022; Xie et al., 2019 2. Regulates cell cycle and lipid homeostasis PPARγ Liver regeneration↓ Reduces TNF and IL-6 in the liver, which are important in the early phase of liver regeneration Collino et al., 2010 CAR Hepatomegaly↑ 1. Activates the expression of the Mdm2 gene to start the cell cycle and restrain apoptosis; Huang et al., 2005, Costa et al., 2005, Hori et al., 2018; Gao et al., 2021 2. YAP can regulate the expression of proliferation genes such as c-Myc and FoxM1 3. GADD45β has been reported to be related to the CAR-associated liver hypertrophy 4. Interacts with YAP-TEAD signaling pathway CAR Liver regeneration↑ YAP activation induced by CAR can regulate the expression of proliferation-related genes such as c-Myc and FoxM1 Costa et al., 2005; Gao et al., 2021 LXR Hepatomegaly Not clear — LXR Liver regeneration↓ LXR activation can reduce liver regeneration capacity during PHx Lo Sasso et al., 2010 FXR Hepatomegaly 1. Fxr-null mice showed increased bile acid level and hepatomegaly Wu et al., 2019; Yang et al., 2007 2. Chronic activation by WAY-362450 induces hepatomegaly by activating cyclin D1 FXR Liver regeneration↑ Induces the expression of Foxm1b and c-Myc de Haan et al., 2021
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