Alternative transporter pathways in patients with untreated early-stage and late-stage primary biliary cirrhosis.
OBJECTIVE
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.
Takeyama
Yasuaki
Y
Department of Gastroenterology and Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
Uehara
Yuko
Y
Inomata
Shinjiro
S
Morihara
Daisuke
D
Nishizawa
Shinya
S
Ueda
Shu-ichi
S
Matsumoto
Teruo
T
Tanaka
Takashi
T
Anan
Akira
A
Nishimura
Hirokatsu
H
Irie
Makoto
M
Iwata
Kaoru
K
Shakado
Satoshi
S
Sohda
Tetsuro
T
Sakisaka
Shotaro
S
D026501:Blotting, Southwestern; D002352:Carrier Proteins / Q000378:metabolism*; D000090702:Constitutive Androstane Receptor; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D002352:Carrier Proteins; D000090702:Constitutive Androstane Receptor; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015345:Oligonucleotide Probes; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C037643:bile acid binding proteins; C099948:fetoprotein transcription factor