Developmental expression of canalicular transporter genes in human liver
Developmental expression of canalicular transporter genes in human liver
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DOI：
10.1016/j.jhep.2005.02.030
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发表时间：
2005-09-01
影响因子：
25.7
通讯作者：
Chang, MH
中科院分区：
文献类型：
--
作者：
Chen, HL;Chen, HL;Chang, MH
背景/目的：BSEP、MRP2 和 MDR3 是介导胆汁分泌的主要肝小管转运蛋白。其在发育过程中人肝脏中的表达尚未见报道。方法：采用实时RT-PCR检测14-20周胎龄胎儿肝脏样本、成人肝脏和胆道闭锁婴儿肝脏样本中BSEP、MDR3、MRP2、NTCP、FIC1和FXR基因的mRNA表达量。对胎儿和成人肝脏进行 BSEP、MDR3 和 MRP2 的免疫组织化学染色。结果：所有测试的基因均在孕中期表达。与成人相比，胎儿肝脏中的 MDR3 和 NTCP 水平显着降低。在胆道闭锁患者中，除 NTCP 外，所有测试的基因均显示出高于成人的平均表达水平，但不具有统计学意义。胎儿肝脏MRP2免疫组化染色为小管状，BSEP显示细胞内和小管状染色，MDR3染色较弱，仅偶尔可见小管状图案。结论：主要小管转运蛋白基因在人胎儿发育过程中的妊娠中期表达，但表达水平和靶向模式不同，表明差异调节和成熟。 (c) 2005 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background/Aims: BSEP, MRP2, and MDR3 are major hepatic canalicular transporters mediating bile secretion. Their expression in human liver during development has not been reported.Methods: Human liver samples from fetus at gestational age 14-20 weeks, adult livers and liver samples of infants with biliary atresia were tested for mRNA expression of BSEP, MDR3, MRP2, NTCP, FIC1, and FXR genes by using real-time RT-PCR. Immunohistochemical staining of BSEP, MDR3, and MRP2 were performed on fetal and adult livers.Results: All the genes tested were expressed at mid-gestational age. MDR3 and NTCP showed significant lower levels in fetal livers compared to adults. In patients with biliary atresia, all the genes tested showed higher mean expression levels than adults except for NTCP, but not statistically significant. The immunohistochemical staining of MRP2 in fetal liver was canalicular, BSEP showed both intracellular and canalicular staining, and MDR3 staining was faint, only occasional canalicular pattern could be seen.Conclusions: The major canalicular transporter genes are expressed at mid-gestational stage during human fetal development, but are different in expression level and targeting pattern, indicating differential regulation and maturation. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.