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Multidrug resistance-associated protein 4 is up-regulated in liver but down-regulated in kidney in obstructive cholestasis in the rat

Denk, Gerald U, Soroka, Carol J, Takeyama, Yasuaki, Chen, Wen-Sheng, Schuetz, John D, Boyer, James L·2004·Journal of Hepatology
DOI 10.1016/j.jhep.2003.12.001
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Abstract

Background/aims Multidrug resistance-associated protein 4 (Mrp4, ABCC4) transports cyclic nucleotides, anti-retroviral compounds, and sulfated bile acids. Mrp4 expression is increased in farnesyl/bile acid receptor knockout mice. Our aim was to investigate Mrp4 expression and function in rat liver and kidney in obstructive cholestasis. Methods Male Sprague-Dawley rats were subjected to bile duct ligation (BDL) or sham-surgery. Animals were sacrificed after 3, 7, and 14 days and tissues were harvested for Western blot analysis, real-time reverse transcriptase-mediated polymerase chain reaction (RT-PCR), and immunohistochemistry. Results Western blot analysis revealed a progressive, more than seven-fold increase (P Conclusions Obstructive cholestasis in rats results in progressive up-regulation of Mrp4 protein in liver but down-regulation in kidney. The absence of corresponding changes in Mrp4 mRNA suggests posttranscriptional mechanisms as predominant regulators of Mrp4 expression in BDL rats.

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Metadata

Authors
Denk, G. U., Soroka, C. J., Takeyama, Y., Chen, W.-S., Schuetz, J. D., & Boyer, J. L.
Venue
Journal of Hepatology
Publisher
Elsevier BV
Published
2004-04
Volume
40
Issue
4
Pages
585-591
ISSN
0168-8278
DOI
10.1016/j.jhep.2003.12.001
Cited by
147
References
1
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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