Alternative transporter pathways in patients with untreated early-stage and late-stage primary biliary cirrhosis
Version of Record online: 25 JUL 2008
© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd
Volume 29, Issue 3, pages 406–414, March 2009
How to Cite
Takeyama, Y., Uehara, Y., Inomata, S., Morihara, D., Nishizawa, S., Ueda, S.-i., Matsumoto, T., Tanaka, T., Anan, A., Nishimura, H., Irie, M., Iwata, K., Shakado, S., Sohda, T. and Sakisaka, S. (2009), Alternative transporter pathways in patients with untreated early-stage and late-stage primary biliary cirrhosis. Liver International, 29: 406–414. doi: 10.1111/j.1478-3231.2008.01846.x
- Issue online: 4 FEB 2009
- Version of Record online: 25 JUL 2008
- Received 13 February 2008Accepted 15 June 2008
- multidrug-resistance protein;
- nuclear hormone receptor;
- primary biliary cirrhosis
Background/Aims: The hepatic expression of bile acid transporters is altered in experimental cholestasis and it is unclear whether regulation exists in human cholestatic diseases. We investigated the expression of genes involved in bile acid detoxification, basolateral export and nuclear factor regulation in untreated primary biliary cirrhosis (PBC).
Methods: Liver tissues were obtained from patients with early-stage and late-stage PBC. The hepatic expression levels of messenger RNAs were determined by the real-time reverse transcription polymerase chain reaction.
Results: The hepatic expression of multidrug-resistance protein 4 messenger RNA was significantly upregulated in early-stage and late-stage PBC patients compared with controls. The hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 messenger RNAs was significantly elevated only in early-stage PBC patients. The hepatic expression levels of farnesoid X receptor, fetoprotein transcription factor and constitutive androstane receptor mRNAs were correlated with those of multidrug-resistance protein 2, multidrug-resistance protein 3 and multidrug-resistance protein 4 respectively.
Conclusions: The hepatic expression of multidrug-resistance protein 4 was enhanced in patients with untreated PBC at all stages. However, the hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 was enhanced only in early-stage patients. The lack of upregulation of these proteins might contribute to the progression of PBC.