Differential developmental regulation of rat liver canalicular membrane transporters Bsep and Mrp2.
Bile formation depends on the active secretion of bile salts and other biliary constituents by specific transporters. Recently two major transporters that contribute to bile formation, the bile salt export pump (Bsep) and multidrug resistance protein-2 (Mrp2), have been cloned. The goal of the present study was to define the expression of Bsep and Mrp2 during rat liver development. mRNA expression as assessed by Northern blot and RT-PCR was higher for Mrp2 (40% of adult) at 21 d fetal age relative to Bsep (<20% of adult). The levels of Mrp2 mRNA increased to approximately 50% of adult at 1 d of life and then rapidly increased to adult levels by 1-3 wk. Nuclear run-on assays for Bsep and Mrp2 showed minimal transcription during fetal life with an increase in transcription in the postnatal period. A different pattern of expression was observed for both Mrp2 and Bsep proteins. During fetal life, there was low expression of Mrp2 and Bsep proteins (<20% of adult) with a gradual increase neonatally reaching adult levels at 4 wk. Thus, we noted a temporal delay between the maximal expression of the mRNA (1-3 wk) and protein (4 wk) for Bsep and Mrp2. These results show that 1) expression (of mRNA and protein) of canalicular transporters is developmentally regulated by both transcriptional and posttranscriptional mechanisms and 2) Mrp2 and Bsep gene expression (mRNA) are differentially regulated.
Tomer
Gitit
G
Laboratory of Developmental and Molecular Hepatology and Division of Pediatric Gastroenterology, Liver and Nutrition, Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA.
Ananthanarayanan
Meenakshisundaram
M
Weymann
Alexander
A
Balasubramanian
Natarajan
N
Suchy
Frederick J
FJ
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics; D005260:Female; D005333:Fetus; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008099:Liver / Q000254:growth & development* / Q000378:metabolism*; D026901:Membrane Transport Proteins; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000235:genetics
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490548:Abcb11 protein, rat; C423013:Abcc2 protein, rat; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger