Heterogeneity of the intrahepatic biliary epithelium.
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 alpha-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.
Glaser
Shannon
S
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, USA. sglaser@neo.tamu.edu
Francis
Heather
H
Demorrow
Sharon
S
Lesage
Gene
G
Fava
Giammarco
G
Marzioni
Marco
M
Venter
Julie
J
Alpini
Gianfranco
G
D015058:1-Naphthylisothiocyanate / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001647:Bile Acids and Salts / Q000502:physiology; D001649:Bile Duct Diseases / Q000473:pathology / Q000503:physiopathology*; D001653:Bile Ducts, Intrahepatic / Q000098:blood supply / Q000166:cytology* / Q000294:innervation / Q000503:physiopathology*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006498:Hepatectomy; D006801:Humans; D008026:Ligation; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology*
D001647:Bile Acids and Salts; D015058:1-Naphthylisothiocyanate; D002251:Carbon Tetrachloride