PHYLOGENIC AND ONTOGENIC EXPRESSION OF HEPATOCELLULAR BILE-ACID TRANSPORT
PHYLOGENIC AND ONTOGENIC EXPRESSION OF HEPATOCELLULAR BILE-ACID TRANSPORT
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DOI：
10.1073/pnas.90.2.435
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发表时间：
1993-01-15
影响因子：
11.1
通讯作者：
MEIER, PJ
中科院分区：
文献类型：
--
作者：
BOYER, JL;HAGENBUCH, B;MEIER, PJ
利用最近从大鼠肝脏中克隆的全长cDNA探针，通过北方分析确定Na+/胆汁酸协同转运蛋白mRNA的胚胎发生和个体发生表达。mRNA在几种哺乳动物物种中检测到，包括大鼠，小鼠和人，但在非哺乳动物物种的肝脏中没有发现，包括鸡，乌龟，青蛙和小溜冰鞋。当胆汁酸转运蛋白在发育中的大鼠肝脏的表达进行了研究，检测到mRNA之间的18和21天的妊娠，在第一次检测时，Na+依赖性胆汁酸转运。两个肝癌细胞系（HTC和HepG 2），其中后者是已知已失去Na+/胆汁酸共转运系统，也没有表达这种转运蛋白的mRNA。最后，当mRNA从较低的脊椎动物（小溜冰鞋）被注射到非洲爪蟾卵母细胞，只有一个钠的非依赖性，氯依赖的胆汁酸运输系统的表达，确认的mRNA的完整性和一致的先前功能研究的胆汁酸运输在这个物种。这些研究结果表明，Na+/胆汁酸共转运mRNA首先在哺乳动物物种中转录，这是一个在大鼠肝脏中哺乳动物胎儿发育后期重现的过程，并且该mRNA在去分化肝细胞中丢失。与此相反，mRNA的多特异性Na+/独立的有机阴离子转运系统的转录在脊椎动物进化的早期。
The phylogenic and ontogenic expression of mRNA for the Na+/bile acid cotransporter was determined by Northern analysis utilizing a full-length cDNA probe recently cloned from rat liver. mRNA was detected in several mammalian species, including rat, mouse, and man, but could not be found in livers from nonmammalian species, including chicken, turtle, frog, and small skate. When expression of the bile acid transporter in developing rat liver was studied, mRNA was detected between 18 and 21 days of gestation, at the time when Na+-dependent bile acid transport is first detected. Two hepatoma cell lines (HTC and HepG2), the latter of which is known to have lost the Na+/bile acid cotransport system, also did not express mRNA for this transporter. Finally, when mRNA from the lower vertebrate (the small skate) was injected into Xenopus oocytes, only a sodium-independent, chloride-dependent transport system for bile acids was expressed, confirming the integrity of the mRNA and consistent with prior functional studies of bile acid transport in this species. These findings establish that the Na+/bile acid cotransport mRNA is first transcribed in mammalian species, a process that is recapitulated late during mammalian fetal development in rat liver, and that this mRNA is lost in dedifferentiated hepatocytes. In contrast, the mRNA for a multispecific Na+/independent organic anion transport system is transcribed earlier in vertebrate evolution.