Regulation of the blood-biliary barrier: Interaction between gap and tight junctions in hepatocytes.
Regulation of the blood-biliary barrier: Interaction between gap and tight junctions in hepatocytes.
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DOI：
10.1007/s00795-003-0220-5
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发表时间：
2003-09-01
期刊：
影响因子：
--
通讯作者：
Sawada, Norimasa
中科院分区：
文献类型：
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作者：
Kojima, Takashi;Yamamoto, Toshinobu;Sawada, Norimasa
肝细胞通过细胞间连接紧密相连，形成肝细胞板。连接由间隙连接、紧密连接和粘附连接组成，桥粒集中在胆小管周围。特别是，紧密连接作为一个屏障，以保持胆汁在胆小管远离血液循环。因此，将肝细胞紧密连接称为血胆屏障是非常合理的。另一方面，肝细胞间隙连接被认为通过其细胞间通讯功能使胆管从中心带到门静脉周围肝细胞有序收缩。因此，间隙和紧密连接可能在胆汁分泌中发挥关键作用，胆汁分泌是肝脏最分化的功能之一：在肝内胆汁淤积（肝脏的一种常见病理状态）中，观察到间隙和紧密连接功能下调，从而导致细胞间通讯受损和紧密连接渗漏。虽然缝隙连接和紧密连接的变化一直被认为是相互独立的，最近的研究结果表明，紧密连接相关蛋白ZO-1和occludin结合连接蛋白的大分子复合物含有缝隙和紧密连接蛋白的协调或相互调节的可能性。本文就体外培养肝细胞间隙连接和紧密连接的相互作用和调控，以及“血胆屏障”的调控机制进行综述，以探讨胆汁淤积的分子发病机制。
Hepatocytes tightly connect with each other by intercellular junctions to form liver cell plates. The junctions composed of gap, tight, and adherens junctions and desmosomes concentrate around bile canaliculi. In particular, tight junctions serve as a barrier to keep bile in bile canaliculi away from the blood circulation. Thus, it is very reasonable to call tight junctions of hepatocytes the blood-biliary barrier. On the other hand, gap junctions of hepatocytes are considered to enable ordered contraction of bile canaculi from centrizonal to periportal hepatocytes by their function of intercellular communication. Gap and tight junctions may thus play a crucial role in bile secretion, one of the most differentiated functions of the liver: In intrahepatic cholestasis, a common pathological condition of the liver, downregulation of gap and tight junctional functions is seen, which results in impaired intercellular communication and in leaky tight junctions. Although the changes in gap and tight junctions had been considered to be independent of each other, recent findings that the tight junction-associated proteins ZO-1 and occludin bind to connexins indicate the possibility of either coordinate or reciprocal regulation of macromolecular complexes containing gap-and tight-junction proteins. In this review, we introduce the interaction and regulation between gap and tight junctions of hepatocytes in vitro and discuss the regulatory mechanisms of the "blood-biliary barrier" to study the molecular pathogenesis of cholestasis.