Dubuisson C, Cresteil D, Desrochers M, Decimo D, Hadchouel M, Jacquemin E
INSERM U 347, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
J Hepatol. 1996 Dec;25(6):932-40. doi: 10.1016/s0168-8278(96)80299-6.
BACKGROUND/AIMS: A cDNA (2.7 kb) encoding a rat liver basolateral Na(+)-independent organic anion transporter (oatp) has recently been cloned. The aim of the present study was to clarify the mechanisms of bile formation during development.
The ontogenic expression of oatp was examined by northern blot analysis and in situ hybridization in rat liver. The expression of oatp in the kidney was also studied in parallel.
In the liver, a 2.5 kb oatp mRNA was first detected in the fetus on day 16 of gestation. The amount of this oatp mRNA remained stable during the perinatal period and increased dramatically after weaning. Other transcripts probably corresponding to oatp-related mRNAs also display a late expression pattern in the perinatal period. In contrast, Na+/taurocholate transporting polypeptide (Ntcp) mRNA was first detected on day 20 of gestation. By in situ hybridization, oatp mRNA was localized into hepatocytes and distributed without lobular heterogeneity. In the kidney, a single 2.4 kb oatp transcript was detected from birth to adult age. This transcript was exclusively distributed in the epithelial cells of the proximal tubules localized in the kidney cortex and the outer medulla.
These results indicate that oatp undergoes a time-related expression in rat liver and kidney during development and that its gene transcription precedes Ntcp gene transcription in the liver. The delayed expression of oatp at the perinatal period may explain in part the immaturity of bile formation and the physiological neonatal cholestasis.
背景/目的：最近克隆了一种编码大鼠肝脏基底外侧非Na⁺依赖性有机阴离子转运体（oatp）的cDNA（2.7 kb）。本研究的目的是阐明发育过程中胆汁形成的机制。
通过Northern印迹分析和原位杂交检测大鼠肝脏中oatp的个体发育表达。同时也对肾脏中oatp的表达进行了研究。
在肝脏中，妊娠第16天的胎儿首次检测到2.5 kb的oatp mRNA。该oatp mRNA的量在围产期保持稳定，断奶后显著增加。其他可能与oatp相关mRNA对应的转录本在围产期也呈现晚期表达模式。相比之下，Na⁺/牛磺胆酸盐转运多肽（Ntcp）mRNA在妊娠第20天首次检测到。通过原位杂交，oatp mRNA定位于肝细胞，且分布无小叶异质性。在肾脏中，从出生到成年期均检测到单一的2.4 kb oatp转录本。该转录本仅分布于肾皮质和外髓质近端小管的上皮细胞中。
这些结果表明，oatp在大鼠肝脏和肾脏发育过程中呈现与时间相关的表达，且其基因转录先于肝脏中Ntcp基因的转录。围产期oatp的延迟表达可能部分解释了胆汁形成的不成熟和生理性新生儿胆汁淤积。
