TY - JOUR
T1 - Differential developmental regulation of rat liver canalicular membrane transporters Bsep and Mrp2
AU - Tomer, Gitit
AU - Ananthanarayanan, Meenakshisundaram
AU - Weymann, Alexander
AU - Balasubramanian, Natarajan
AU - Suchy, Frederick J.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - 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 ∼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.
AB - 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 ∼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.
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U2 - 10.1203/00006450-200302000-00014
DO - 10.1203/00006450-200302000-00014
M3 - Article
C2 - 12538788
AN - SCOPUS:0037313267
SN - 0031-3998
VL - 53
SP - 288
EP - 294
JO - Pediatric Research
JF - Pediatric Research
IS - 2
ER -