New molecular insights into the mechanisms of cholestasis

被引：223

作者：

Wagner, Martin ^{[1
]}

Zollner, Gernot ^{[1
]}

Trauner, Michael ^{[1
]}

机构：

[1] Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Lab Expt & Mol Hepatol, A-8036 Graz, Austria

来源：

JOURNAL OF HEPATOLOGY | 2009年 / 51卷 / 03期

关键词：

Cholestasis; Bile acids; Hepatobiliary transporters; Nuclear receptors; PRIMARY BILIARY-CIRRHOSIS; SALT EXPORT PUMP; PRIMARY SCLEROSING CHOLANGITIS; FARNESOID-X-RECEPTOR; FAMILIAL INTRAHEPATIC CHOLESTASIS; BILE-ACID SYNTHESIS; HEPATOBILIARY TRANSPORTER EXPRESSION; CONSTITUTIVE ANDROSTANE RECEPTOR; ENRICHED TRANSCRIPTION FACTORS; ATP-BINDING-CASSETTE;

D O I：

10.1016/j.jhep.2009.05.012

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibility and disease progression in acquired cholestatic disorders. Cholestasis is associated with complex transcriptional and post-transcriptional alterations of hepatobiliary transporters and enzymes participating in bile formation. Ligand-activated nuclear receptors for bile acids and other biliary compounds play a key role in the regulation of genes required for bile formation. Pharmacological interventions in cholestasis may aim at modulating such novel regulatory pathways. This review will summarize the principles of molecular alterations in cholestasis and will give an overview of potential clinical implications. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：565 / 580

页数：16

共 192 条

[1] Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1 [J].