title: Structural and functional hepatocyte polarity and liver disease.
abstract: 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.
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, UK; UCL Institute of Child Health, London, UK; Great Ormond Street Hospital, London, UK. Electronic address: p.gissen@ucl.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Gissen
authors.affiliation: Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States.
authors.forename: Irwin M
authors.initials: IM
authors.lastname: Arias
mesh_terms: D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D019108:Tight Junctions
keywords: Canalicular diseases; Cholestasis; Hepatocyte biology; Hepatocyte polarity; Inherited liver diseases