The ecto-nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver
The ecto-nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver
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DOI：
10.1053/jhep.2002.36823
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发表时间：
2002-11-01
期刊：
影响因子：
13.5
通讯作者：
Sévigny, J
中科院分区：
文献类型：
--
作者：
Dranoff, JA;Kruglov, EA;Sévigny, J
细胞外核苷酸调节多种生物学功能，并且在调节肝脏代谢、肝血流量和胆汁分泌中是重要的。外三磷酸核苷二磷酸水解酶（NTPDases）水解细胞外核苷酸，因此是核苷酸介导的信号转导的潜在调节剂。为了检验这一点，我们对比了2个特征性的膜结合NTPDase NTPDase 1和NTPDase 2在大鼠肝脏内的结构和功能分布。使用共聚焦免疫荧光、免疫电镜、逆转录聚合酶链反应、北方印迹分析、Western印迹分析和功能测定确定NTPDase2的肝脏表达并与NTPDase1进行对比。NTPD酶2在肝内胆管周围的门静脉周围区域表达，而NTPD酶I在肝动脉、门静脉和肝中央静脉中发现，与其已知的血管分布一致。NTPD酶2的功能和分子表达显示在门静脉成纤维细胞附近的胆管上皮基底外侧膜。总之，NTPDase2在肝内胆管周围的一个新的细胞区室中表达，即门静脉成纤维细胞。这种分布可能代表了一种以前未被认识的机制，用于调节胆管和其他上皮细胞中的核苷酸信号。
Extracellular nucleotides regulate diverse biological functions and are important in the regulation of liver metabolism, hepatic blood flow, and bile secretion. Ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) hydrolyze extracellular nucleotides and are therefore potential regulators of nucleotide-mediated signaling. To examine this, we have contrasted the structural and functional distributions of the 2 characterized membrane-bound NTPDases NTPDase1 and NTPDase2 within the rat liver. Hepatic expression of NTPDase2 was determined and contrasted to NTPDase1 using confocal immunofluorescence, immunoelectron microscopy, reverse-transcription polymerase chain reaction, Northern blot analysis, Western blot analysis, and functional assays. NTPDase2 was expressed in the periportal region surrounding intrahepatic bile ducts, whereas NTPDase I was found in hepatic arteries, portal veins, and hepatic central veins, consistent with its known vascular distribution. Functional and molecular expression of NTPDase2 was shown in portal fibroblasts near basolateral membranes of bile duct epithelia. In conclusion, NTPDase2 is expressed in a novel cellular compartment surrounding intrahepatic bile ducts, namely portal fibroblasts. This distribution may represent a previously unrecognized mechanism for regulation of nucleotide signaling in bile ducts and other epithelia.