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Cited by 1,379

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity

Open access
Staudinger, Jeff L., Goodwin, Bryan, Jones, Stacey A., Hawkins-Brown, Diane, MacKenzie, Kathleen I., LaTour, Anne, Liu, Yaping, Klaassen, Curtis D., Brown, Kathleen K., Reinhard, John, Willson, Timothy M., Koller, Beverly H., Kliewer, Steven A.·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.051551698
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Abstract

The pregnane X receptor (PXR) is the molecular target for catatoxic steroids such as pregnenolone 16α-carbonitrile (PCN), which induce cytochrome P450 3A ( CYP3A ) expression and protect the body from harmful chemicals. In this study, we demonstrate that PXR is activated by the toxic bile acid lithocholic acid (LCA) and its 3-keto metabolite. Furthermore, we show that PXR regulates the expression of genes involved in the biosynthesis, transport, and metabolism of bile acids including cholesterol 7α-hydroxylase ( Cyp7a1 ) and the Na + -independent organic anion transporter 2 ( Oatp2 ). Finally, we demonstrate that activation of PXR protects against severe liver damage induced by LCA. Based on these data, we propose that PXR serves as a physiological sensor of LCA, and coordinately regulates gene expression to reduce the concentrations of this toxic bile acid. These findings suggest that PXR agonists may prove useful in the treatment of human cholestatic liver disease.

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Metadata

Authors
Staudinger, J. L., Goodwin, B., Jones, S. A., Hawkins-Brown, D., MacKenzie, K. I., LaTour, A., Liu, Y., Klaassen, C. D., Brown, K. K., Reinhard, J., Willson, T. M., Koller, B. H., & Kliewer, S. A.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2001-03-13
Volume
98
Issue
6
Pages
3369-3374
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.051551698
OpenAlex
W2021444563
Cited by
1,379
References
2
FWCI
32.70
Type
journal article
Language
en
Open access
green

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