Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver
Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver
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DOI：
10.1053/gast.1996.v110.pm8613073
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发表时间：
1996-05-01
期刊：
影响因子：
29.4
通讯作者：
LaRusso, NF
中科院分区：
文献类型：
--
作者：
Alpini, G;Roberts, S;LaRusso, NF
背景和目标：虽然肝细胞的小叶异质性已经确立，但有限的数据表明，胆管上皮细胞或胆管细胞沿沿着正常肝内胆管树是异质的。因此，我们测试的假设，胆管细胞的结构和功能的异质性在正常大鼠的胆道。研究方法：在正常大鼠中进行了一系列原位和体外实验，使用互补的形态测量，分子和功能的方法。结果如下：原位形态测量显示：（1）肝内胆管外径不均匀（5-200 μ m）;（2）胆管内壁单个胆管细胞面积不均匀（3-80 μ m）;（3）胆管直径与胆管细胞面积之间存在显著关系。使用我们开发的一种新方法，我们分离出三个小，中，大胆管细胞亚群，并在分子和功能水平上进行比较。两个胆管细胞特异性基因（γ-谷氨酰转肽酶和细胞角蛋白19）的表达是相似的三个亚群。与此相反，促胰液素受体，Cl-/HCO 3-交换，囊性纤维化跨膜传导调节信使RNA的差异表达，存在于中型和大型，但不是小型胆管细胞。在功能水平上，腺苷3 '，5'-环磷酸和细胞内pH值的反应和Cl-/HCO 3-交换活性增强分泌素在中型和大型，但不是小型胆管细胞。结论：这些数据表明，胆管细胞是形态和功能异质沿着正常肝内胆管树，并建议分泌素调节的水和电解质的运输主要发生在中型和大型管道。
Background & Aims: While the lobular heterogeneity of hepatocytes is established, limited data suggest that bile duct epithelial cells, or cholangiocytes, are heterogeneous along the normal intrahepatic biliary tree. Thus, we tested the hypothesis that cholangiocytes are structurally and functionally heterogeneous in the biliary tract of normal rats. Methods: A series of in situ and in vitro experiments was performed in normal rats using complementary morphometric, molecular, and functional approaches. Results: In situ morphometry showed that (1) intrahepatic bile ducts are heterogeneous in external diameter (5-200 mu m); (2) individual cholangiocytes lining bile ducts are heterogeneous in area (3-80 mu m(2)); and (3) a significant relationship exists between bile duct diameter and cholangiocyte area. Using a novel approach developed by us, we isolated three subpopulations of small, medium, and large cholangiocytes and compared them at the molecular and functional level. The expression of two cholangiocyte-specific genes (gamma-glutamyl transpeptidase and cytokeratin 19) was similar among the three subpopulations. In contrast, secretin receptor, Cl-/HCO3- exchanger, and cystic fibrosis transmembrane conductance regulator messenger RNAs were differentially expressed, being present in medium and large but not small cholangiocytes. At the functional level, adenosine 3', 5'-cyclic monophosphate and intracellular pH responses and Cl-/HCO3- exchanger activity was enhanced by secretin in medium and large but not small cholangiocytes. Conclusions: These data indicate that cholangiocytes are morphologically and functionally heterogeneous along the normal intrahepatic biliary tree and suggest that secretin-regulated transport of water and electrolytes occurs principally in medium and large ducts.