Sustained upregulation of sodium taurocholate cotransporting polypeptide and bile salt export pump and downregulation of cholesterol 7α-hydroxylase in the liver of patients with end-stage primary biliary cirrhosis.

Abstract

To examine the mRNA expression of hepatobiliary transporters in primary biliary cirrhosis (PBC) patients and to compare bile acid absorption, synthesis, and efflux in patients with non-end-stage and end-stage PBC, we obtained liver samples from PBC patients by percutaneous needle biopsy. End-stage PBC was defined as follows: histological stage IV; cirrhosis; serum total bilirubin, ≥4.0 mg/dl; and Child-Pugh Class C. The mRNA expression levels of sodium taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and hepatic cholesterol 7α-hydroxylase (CYP7A1) were significantly higher in the PBC patients than in the controls (P < 0.01). The mRNA levels of NTCP and BSEP were significantly higher in the end-stage PBC patients than in the controls (P < 0.01). However, hepatic CYP7A1 mRNA expression decreased significantly (by 70%) in the patients with end-stage PBC as compared to the controls and the patients with non-end-stage PBC (P < 0.01). The hepatic expression of transporters mediating bile acid influx and efflux showed sustained elevation, whereas that of the rate-limiting enzyme for bile acid biosynthesis was attenuated in the end-stage PBC patients. Thus, mechanisms may be present preventing the accumulation of toxic bile acids in the hepatocytes of end-stage PBC patients.

• Authors: Yasuaki Takeyama, Kazuko Kanegae, Shinjiro Inomata, Kazuhide Takata, Takashi Tanaka, Shu-Ichi Ueda, Keiji Yokoyama, Daisuke Morihara, Shinya Nishizawa, Akira Anan, Makoto Irie, Kaoru Iwata, Satoshi Shakado, Tetsuro Sohda, Shotaro Sakisaka
• Journal: Medical molecular morphology (Med Mol Morphol) Vol. 43 Issue 3 Pg. 134-8 (Sep 2010) ISSN: 1860-1499 [Electronic] Japan
• PMID: 20857261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB11 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 11
• ATP-Binding Cassette Transporters
• Bile Acids and Salts
• Organic Anion Transporters, Sodium-Dependent
• RNA, Messenger
• Symporters
• sodium-bile acid cotransporter
• CYP7A1 protein, human
• Cholesterol 7-alpha-Hydroxylase

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 11
• ATP-Binding Cassette Transporters (biosynthesis, genetics)
• Bile Acids and Salts (metabolism)
• Cholesterol 7-alpha-Hydroxylase (biosynthesis, genetics)
• Down-Regulation
• End Stage Liver Disease (metabolism)
• Humans
• Liver (metabolism)
• Liver Cirrhosis, Biliary (metabolism)
• Organic Anion Transporters, Sodium-Dependent (biosynthesis, genetics)
• RNA, Messenger (biosynthesis)
• Symporters (biosynthesis, genetics)
• Up-Regulation