The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease.
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.
Lam
Ping
P
Liver Center, Yale University School of Medicine, New Haven, Connecticut 06510-8019, USA. ping.lam@yale.edu
Soroka
Carol J
CJ
Boyer
James L
JL
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology; D001648:Bile Canaliculi / Q000502:physiology; D002780:Cholestasis, Intrahepatic / Q000235:genetics / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000502:physiology; D006031:Glycosylation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009154:Mutation; D010766:Phosphorylation; D054875:Ubiquitination / Q000502:physiology
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts