Epithelial–Mesenchymal Interactions in Biliary Diseases

Luca Fabris; Mario Strazzabosco

doi:10.1055/s-0031-1272832

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2011; 31(1): 011-032
DOI: 10.1055/s-0031-1272832

Epithelial–Mesenchymal Interactions in Biliary Diseases

Luca Fabris¹ ^, ² , Mario Strazzabosco² ^, ³ ^, ⁴

¹Department of Surgical and Gastroenterological Sciences, University of Padua, Padova, Italy
²Center for Liver Research (CeLiveR), Bergamo, Italy
³Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut
⁴Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy

Abstract

ABSTRACT

In most cholangiopathies, liver diseases of different etiologies in which the biliary epithelium is the primary target in the pathogenic sequence, the central mechanism involves inflammation. Inflammation, characterized by pleomorphic peribiliary infiltrate containing fibroblasts, macrophages, lymphocytes, as well as endothelial cells and pericytes, is associated to the emergence of “reactive cholangiocytes.” These biliary cells do not possess bile secretory functions, are in contiguity with terminal cholangioles, and are of a less-differentiated phenotype. They have acquired several mesenchymal properties, including motility and ability to secrete a vast number of proinflammatory chemo/cytokines and growth factors along with de novo expression of a rich receptor machinery. These functional properties enable reactive cholangiocytes to establish intimate contacts and to mutually exchange a variety of paracrine signals with the different mesenchymal cell types populating the portal infiltrate. The extensive crosstalk between the epithelial and mesenchymal compartments is the driver of liver repair mechanisms in cholangiopathies, ultimately evolving toward portal fibrosis. Herein, the authors first review the properties of the different cell types involved in their interaction, and then analyze the underlying molecular mechanisms as they relate to liver repair in cholangiopathies.

KEYWORDS

Cholangiopathies - cholangiocytes - ductular reaction - myofibroblasts - endothelial cells

Full Text

References

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Mario StrazzaboscoM.D. Ph.D.

Department of Internal Medicine, Section of Digestive Diseases

Yale University School of Medicine, 333 Cedar Street LMP 1080, New Haven, CT 06520

Email: mario.strazzabosco@yale.edu