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Cited by 41Liver physiology and pathologyHippo pathway signaling and YAP/TAZDrug-Induced Hepatotoxicity and Protection

Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially via yes-associated protein activation

Open access
Gao, Yue, Fan, Shicheng, Li, Hua, Jiang, Yiming, Yao, Xinpeng, Zhu, Shuguang, Yang, Xiao, Wang, Ruimin +4 more·2021·Acta Pharmaceutica Sinica B
DOI 10.1016/j.apsb.2020.11.021PMC PMC7982502
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Abstract

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67+ cells around portal vein (PV) area. The protein levels of YAP and its downstream targets were upregulated in TCPOBOP-treated mice and YAP translocation can be induced by CAR activation. Co-immunoprecipitation results suggested a potential protein–protein interaction of CAR and YAP. However, CAR activation-induced hepatomegaly can still be observed in liver-specific YAP-deficient (Yap–/–) mice. In summary, CAR activation promotes hepatomegaly and liver regeneration partially by inducing YAP translocation and interaction with YAP signaling pathway, which provides new insights to further understand the physiological functions of CAR.

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References 34 · Cited by 41

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Authors
Gao, Y., Fan, S., Li, H., Jiang, Y., Yao, X., Zhu, S., Yang, X., Wang, R., Tian, J., Gonzalez, F. J., Huang, M., & Bi, H.
Affiliations
  • Sun Yat-sen University (CN)
  • National Cancer Institute (US)
Corresponding author
  • Huang, Min
  • Bi, Huichang
ORCID
Venue
Acta Pharmaceutica Sinica B
Publisher
Elsevier BV
Published
2021-03
Volume
11
Issue
3
Pages
727-737
ISSN
2211-3835 (ISSN-L)
DOI
10.1016/j.apsb.2020.11.021
PMC
PMC7982502
OpenAlex
W3108739829
Cited by
41
References
34
Citations by year
2026: 5 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 10 · 2021: 1
FWCI
2.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Pharmaceutica Sinica B (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Higher Education Discipline Innovation Project (B16047)
  • Guangdong Provincial Pearl River Talents Program (2017BT01Y093)
  • National Key Research and Development Program of China (2017YFE0109900)
  • National Natural Science Foundation of China (81973392, 82025034)
  • Guangdong Provincial Key Laboratory of Construction Foundation (2017B030314030)
  • Shenzhen Science and Technology Innovation Program (KQTD20190929174023858)
  • Natural Science Foundation of Guangdong Province (2017A030311018)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
constitutive androstane receptor, hepatomegaly, liver regeneration, YAP, TCPOBOP, partial hepatectomy, hepatocyte proliferation, nuclear receptor signaling

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