The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease

被引:73
作者
Lam, Ping [1 ]
Soroka, Carol J. [1 ]
Boyer, James L. [1 ]
机构
[1] Yale Univ, Sch Med, Ctr Liver, New Haven, CT 06510 USA
关键词
Cholestasis; progressive familial intrahepatic cholestasis; bile salt export pump (BSEP) mutations; polymorphisms; ATP-binding cassette (ABC) transporters; trafficking; recycling; ubiquitination; FAMILIAL INTRAHEPATIC CHOLESTASIS; BINDING CASSETTE TRANSPORTERS; CANALICULAR MEMBRANE-VESICLES; RAT HEPATOCYTE COUPLETS; FARNESOID-X-RECEPTOR; CANINE KIDNEY-CELLS; MDCK-II CELLS; P-GLYCOPROTEIN; KNOCKOUT MICE; NUCLEAR RECEPTOR;
D O I
10.1055/s-0030-1253222
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The primary transporter responsible for bile salt secretion is the bile salt export pump (BSEP, ABCB11), a member of the ATP-binding cassette (ABC) superfamily, which is located at the bile canalicular apical domain of hepatocytes. In humans, BSEP deficiency results in several different genetic forms of cholestasis, which include progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), as well as other acquired forms of cholestasis such as drug-induced cholestasis (DIC) and intrahepatic cholestasis of pregnancy (ICP). Because bile salts play a pivotal role in a wide range of physiologic and pathophysiologic processes, regulation of BSEP expression has been a subject of intense research. The authors briefly describe the molecular characteristics of BSEP and then summarize what is known about its role in the pathogenesis of genetic and acquired cholestatic disorders, emphasizing experimental observations from animal models and cell culture in vitro systems.
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页码:125 / 133
页数:9
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