Structural and functional hepatocyte polarity and liver disease.
Structural and functional hepatocyte polarity and liver disease.
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DOI：
10.1016/j.jhep.2015.06.015
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发表时间：
2015-10
影响因子：
25.7
通讯作者：
Arias IM
中科院分区：
文献类型：
--
作者：
Gissen P;Arias IM
肝细胞形成至关重要的细胞层，将肝窦血液与胆小管分开。它们具有独特组织的极性，其基底膜面向肝窦内皮细胞，而一个或多个顶极可以与直接相对的肝细胞共同形成多个胆小管。肝细胞极性的建立和维持对于肝细胞的许多功能至关重要，并且需要细胞粘附分子、细胞连接、细胞骨架、细胞外基质和细胞内运输机制之间精心策划的合作。肝细胞极化过程需要能量，如果异常，可能会导致严重的肝脏疾病。许多影响紧密连接和细胞内运输蛋白的遗传性疾病已被描述，并证明其临床和病理生理学特征与小管 ABC 转运蛋白缺陷引起的遗传性胆汁淤积性肝病重叠。因此，结构和功能成分都有助于最终的肝细胞极性表型。许多获得性肝病的目标是决定肝细胞极性的因素，例如连接蛋白。肝细胞去极化经常发生，但很少被识别，因为苏木精-伊红染色不能识别胆小管。然而，这些缺陷背后的分子机制尚不清楚。在这里，我们的目标是提供有关决定肝细胞极性的关键因素及其在遗传性和获得性疾病中如何影响的最新信息。
Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases.