p53‐mediated regulation of bile acid disposition attenuates cholic acid‐induced cholestasis in mice Article Swipe
Pan Chen
,
Dongshun Li
,
Yixin Chen
,
Jiahong Sun
,
Kaili Fu
,
Lihuan Guan
,
Huizhen Zhang
,
Yiming Jiang
,
Xi Li
,
Xuezhen Zeng
,
Xiao Chen
,
Min Huang
,
Huichang Bi
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1111/bph.14035
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1111/bph.14035
Background and Purpose The tumour suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have demonstrated that it contributes to metabolic diseases. Here, we investigated the role of p53 in the regulation of bile acid disposition and cholestasis. Experimental Approach The bile acid disposition‐related gene expression profile affected by p53 activation was assessed in mouse primary hepatocytes with p53 depletion and in Trp53 ‐null mice. Dual luciferase reporter assay was used to detect the transcriptional activities of target genes. Anticholestatic effects of p53 activator doxorubicin were investigated in a 0.5% cholic acid‐fed mouse model of cholestasis. Changes in bile acids were evaluated using metabolomics analysis. Key Results Doxorubicin‐mediated p53 activation induced Cyp2b10 , Sult2a1 and Abcc2/3/4 expression in mice in vitro and in vivo . ABCC3 and CYP2B6 (human orthologue of Cyp2b10 ) were identified as direct p53 target genes. Doxorubicin attenuated cholic acid‐induced cholestasis in mice, as demonstrated by shrunken gall bladder, decreased serum total bile acid and total bilirubin levels and alkaline phosphatase activity. Targeted metabolomics analysis revealed that doxorubicin enhanced the excretion of bile acid metabolites from serum and liver to intestine and faeces. Up‐regulation of Cyp2b10 , Sult2a1 and Abcc2/3/4 expression was further confirmed in cholestatic mice. Cholic acid‐induced cholestatic injury was aggravated in p53‐deficient mice and levels of bile acid in intestine and faeces were decreased. Conclusions and Implications Our findings suggest a novel role of p53 in promoting bile acid disposition and alleviating cholestatic syndrome, which provides a potential therapeutic target for cholestasis.
Related Topics
Concepts
Cholic acid
Cholestasis
Bile acid
Lithocholic acid
Chenodeoxycholic acid
Cholesterol 7 alpha-hydroxylase
Internal medicine
Taurocholic acid
Biology
Endocrinology
Multidrug resistance-associated protein 2
Biochemistry
Chemistry
Medicine
ATP-binding cassette transporter
Gene
Transporter
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/bph.14035
- https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.14035
- OA Status
- bronze
- Cited By
- 23
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2756280784
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2756280784Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/bph.14035Digital Object Identifier
- Title
-
p53‐mediated regulation of bile acid disposition attenuates cholic acid‐induced cholestasis in miceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-09-14Full publication date if available
- Authors
-
Pan Chen, Dongshun Li, Yixin Chen, Jiahong Sun, Kaili Fu, Lihuan Guan, Huizhen Zhang, Yiming Jiang, Xi Li, Xuezhen Zeng, Xiao Chen, Min Huang, Huichang BiList of authors in order
- Landing page
-
https://doi.org/10.1111/bph.14035Publisher landing page
- PDF URL
-
https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.14035Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.14035Direct OA link when available
- Concepts
-
Cholic acid, Cholestasis, Bile acid, Lithocholic acid, Chenodeoxycholic acid, Cholesterol 7 alpha-hydroxylase, Internal medicine, Taurocholic acid, Biology, Endocrinology, Multidrug resistance-associated protein 2, Biochemistry, Chemistry, Medicine, ATP-binding cassette transporter, Gene, TransporterTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
23Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 3, 2023: 3, 2022: 2, 2021: 3Per-year citation counts (last 5 years)
- References (count)
-
54Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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