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World J Gastroenterol. Jun 14, 2006; 12(22): 3523-3536
Published online Jun 14, 2006. doi: 10.3748/wjg.v12.i22.3523
Heterogeneity of the intrahepatic biliary epithelium
Shannon Glaser, Heather Francis, Sharon DeMorrow, Gene LeSage, Giammarco Fava, Marco Marzioni, Julie Venter, Gianfranco Alpini
Shannon Glaser, Department of Medicine, Division of Research and Education, Scott & White Memorial Hospital and The Texas A&M University System Health Science Center, College of Medicine, Temple, TX, United States
Heather Francis, Sharon DeMorrow, Division of Research and Education, Scott & White Memorial Hospital and The Texas A&M University System Health Science Center, College of Medicine, Temple, TX, United States
Gene LeSage, University of Texas at Houston Medical School, Houston, TX. United States
Giammarco Fava, Marco Marzioni, Department of Gastroenterology, Università Politecnica delle Marche, Azienda Ospedaliera “Ospedali Riuniti di Ancona”, Ancona, Italy
Julie Venter, Department of Medicine, Scott & White Memorial Hospital and The Texas A&M University System Health Science Center, College of Medicine, Temple, TX, United States
Gianfranco Alpini, Central Texas Veterans Health Care System, Department of Medicine, Systems Biology and Translational Medicine, Scott & White Memorial Hospital and The Texas A&M University System Health Science Center, College of Medicine, Temple, TX, United States
Author contributions: All authors contributed equally to the work.
Supported by a grant award from Scott & White Hospital and The Texas A&M University System Health Science Center, a VA Merit Award, a VA Research Scholar Award and the NIH grants DK58411 and DK062975 to Dr. Alpini, by grant awards to Shannon Glaser and Heather Francis from Scott & White Hospital.
Correspondence to: Shannon Glaser, MS, Department of Medicine, Division of R&E, Scott and White Memorial Hospital and The Texas A&M University System Health Science Center College of Medicine, MRB, 702 South West H.K. Dodgen Loop, Temple, Texas 76504, United States. sglaser@neo.tamu.edu
Telephone: +1-254-7427044 Fax: +1-254-7245944
Received: January 22, 2006
Revised: May 10, 2006
Accepted: May 18, 2006
Published online: June 14, 2006
Abstract

The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids, carbon tetrachloride (CCl4) or α-naphthylisothiocyanate (ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium. These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts. Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies.

Keywords: cAMP; Gastrointestinal hormones; Growth factors; Mitosis; Nerves