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首页> 外文期刊>American Journal of Physiology >Asynchronous expression and colocalization of Bsep and Mrp2 during development of rat liver.
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Asynchronous expression and colocalization of Bsep and Mrp2 during development of rat liver.

机译：大鼠肝脏发育过程中Bsep和Mrp2的异步表达和共定位。

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摘要

In the liver, function of the bile salt export pump (Bsep), a major canalicular exporter of bile salts, is complemented by activity of the multidrug resistance protein 2 (Mrp2), a canalicular organic anions transporter. Mrp2 was found capable of transporting various anticancer drugs out of cells, eventually undermining their therapeutic potential and contributing to multidrug resistance. We employed a RT-PCR, immunoblotting, and immunofluorescence to examine their gene, protein expression, and distribution of antigenic sites in the rat liver during development from 16-day-old fetus to adult animal. Bsep mRNA was almost undetectable before birth. It was first clearly expressed in the liver of newborn rats. On the contrary, Mrp2 mRNA was seen before birth, although at low levels. In concert with mRNA expression, Bsep protein was undetectable before birth, while Mrp2 protein was already expressed. Both proteins were clearly detectable in the postnatal period. Confocal immunofluorescent microscopy showed asynchronous appearance of Bsep and Mrp2 proteins during development but their colocalization in the bile canaliculi once each one is expressed. During the gestational period, a weak immunofluorescence for Mrp2 was observed only in livers of 16-day-old embryos. No fluorescence for Bsep was seen. Both proteins were clearly visualizable after birth, although the pattern of immunostaining varied. These findings provide molecular evidence that expression of both Bsep and Mrp2 during development is transcriptionally regulated. They also point out the differences in relevance to the liver function of the systems responsible for canalicular transport of bile salts versus organic anions.
机译：在肝脏中，胆汁盐的主要出口通道胆盐输出泵（Bsep）的功能由多药抗性蛋白2（Mrp2）（一种胆管有机阴离子转运蛋白）的活性所补充。人们发现Mrp2能够将各种抗癌药物转运出细胞，最终破坏了它们的治疗潜能并促进了多药耐药性。我们采用了RT-PCR，免疫印迹和免疫荧光的方法，研究了它们在从16天大的胎儿发育为成年动物的过程中在大鼠肝脏中的基因，蛋白质表达和抗原性位点的分布。出生前几乎检测不到Bsep mRNA。它首先在新生大鼠的肝脏中清晰表达。相反，Mrp2 mRNA在出生前就已发现，尽管水平很低。与mRNA表达一致，出生前无法检测到Bsep蛋白，而Mrp2蛋白已经表达。两种蛋白在出生后均明显可检出。共聚焦免疫荧光显微镜检查显示发育过程中Bsep和Mrp2蛋白异步出现，但是一旦表达，它们在胆小管中共定位。在妊娠期，仅在16日龄胚胎的肝脏中观察到了针对Mrp2的弱免疫荧光。没有观察到Bsep的荧光。两种蛋白在出生后都清晰可见，尽管免疫染色的方式各不相同。这些发现提供了分子证据，表明发育过程中Bsep和Mrp2的表达均受转录调控。他们还指出了与胆管盐和有机阴离子的小管转运有关的系统与肝功能的相关性差异。

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