The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis
Open accessAbstract
Farnesoid X receptor (FXR) is a bile acid-activated transcription factor that is a member of the nuclear hormone receptor superfamily. Fxr-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct-ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in significant reductions in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, as well as other markers of liver damage. Rats that received GW4064 treatment also had decreased incidence and extent of necrosis, decreased inflammatory cell infiltration, and decreased bile duct proliferation. Analysis of gene expression in livers from GW4064-treated cholestatic rats revealed decreased expression of bile acid biosynthetic genes and increased expression of genes involved in bile acid transport, including the phospholipid flippase MDR2. The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease.
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Cites
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Self-citationA regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
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Self-citation
Cited by
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
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Pleiotropic Roles of Bile Acids in Metabolism
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Bile acid signaling in metabolic disease and drug therapy
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LXRS AND FXR: The Yin and Yang of Cholesterol and Fat Metabolism
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Metadata
- Authors
- Liu, Y., Binz, J., Numerick, M. J., Dennis, S., Luo, G., Desai, B., MacKenzie, K. I., Mansfield, T. A., Kliewer, S. A., Goodwin, B., & Jones, S. A.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-12-01
- Volume
- 112
- Issue
- 11
- Pages
- 1678-1687
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2156933673
- Cited by
- 398
- References
- 46
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Liu, Y., Binz, J., Numerick, M. J., Dennis, S., Luo, G., Desai, B., MacKenzie, K. I., Mansfield, T. A., Kliewer, S. A., Goodwin, B., & Jones, S. A. (2003). Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. Journal of Clinical Investigation. https://doi.org/10.1172/jci18945
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