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Alternative transporter pathways in patients with untreated early‐stage and late‐stage primary biliary cirrhosis
Author(s) -
Takeyama Yasuaki,
Uehara Yuko,
Inomata Shinjiro,
Morihara Daisuke,
Nishizawa Shinya,
Ueda Shuichi,
Matsumoto Teruo,
Tanaka Takashi,
Anan Akira,
Nishimura Hirokatsu,
Irie Makoto,
Iwata Kaoru,
Shakado Satoshi,
Sohda Tetsuro,
Sakisaka Shotaro
Publication year - 2009
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2008.01846.x
Subject(s) - multidrug resistance associated protein 2 , multiple drug resistance , primary biliary cirrhosis , downregulation and upregulation , biology , cholestasis , cirrhosis , gas6 , messenger rna , cancer research , farnesoid x receptor , abcg2 , medicine , biliary cirrhosis , bile salt export pump , endocrinology , transporter , drug resistance , transcription factor , receptor , immunology , nuclear receptor , atp binding cassette transporter , gene , biochemistry , receptor tyrosine kinase , genetics , antibody , autoimmune disease
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.