The Pathophysiology of Biliary Epithelia

Preface, 1. Normal and Abnormal Development of the Biliary Tree, Anatomy, The Hepatic Primordium, The Intrahepatic Biliary Tree, Three-Dimensional Architecture of the Intrahepatic Biliary Tree, Bile Ductules and the Canals of Hering, Peribiliary Glands, Abnormal Development of the Biliary Tree, 2. Human Liver Stem Cells: Recent Developments, Liver Regeneration, Hematopoietic-Derived Stem Cells, In Vitro Studies, Factors Which Control Stem Cell Differentiation, 3. Vascularization of the Intrahepatic Biliary Tree and Its Role in the Regulation of Cholangiocyte Growth, Background and Experimental Approach, Rearrangement of PBP during Cholangiocyte Proliferation, Role of VEGF in the Regulation of Vascular Proliferation during Cholangiocyte Growth, 4. Ultra-Structural Analysis of the Intrahepatic Bile Duct System, Ultrastructure of Bile Ducts, 5. Three-Dimensional Reconstruction of the Rat Intrahepatic Biliary Tree: Physiological Implications, Micro-CT, Quantitative Assessment of the Intrahepatic Biliary Tree, Segment-by-Segment Analysis of the Reconstructed Biliary Tree, Number and Length of the Bile Duct Interbranch Segments, Diameter of Bile Duct Segment, Biliary Tree Volume, Heterogeneity of Bile Flow along the Biliary Tree Axis, Type of Anatomic Remodeling, Origin and Fate of the Newly Formed Bile Ducts, Inducers of Cholangiocyte Proliferation, 6. Cholangiocyte Ion Channels: Targets for Drug Development, Mechanisms of Ion Transport—Properties of Ion Channels, Cellular Strategies for Secretion—Transepithelial Cl- Transport, Cyclic AMP-Independent Regulation of Secretion, Regulation of the Number and Types of Ion Channels in the Plasma Membrane, Effects of Cytokines and Nitric Oxide on Bicarbonate Secretion by Cholangiocytes, 7. Inflammatory Cytokines and Cholangiocyte Secretory Function, Nitric Oxide and Cholangiocyte Secretory Function, 8. Hormonal Regulation of Cholangiocyte Secretion, Secretin, Acetylcholine, Vasoactive Intestinal Peptide (VIP), Bombesin, Somatostatin, Gastrin and Insulin, Estrogens, Corticosteroids, 9. Purinergic Regulation of Bile Ductular Secretion, Introduction to P2 Receptors and Purinergic Signaling, P2Y Receptor Actions in Epithelia, Identification of P2Y Receptors in Isolated Cell Models of Biliary Epithelia, Use of Polarized Cholangiocyte Cell Models to Study Nucleotide-Mediated Signaling in Biliary Epithelia, Use of in Vitro Tissue Culture Models to Study Nucleotide-Mediated Signaling in Biliary Epithelia, Potential Roles of Nucleotide Release to Mediate Paracrine Signaling between Hepatocytes and Biliary Epithelia, 10. Calcium Signaling in Cholangiocytes, Molecular Basis for Calcium Signaling in Bile Duct Cells, Calcium Signaling Patterns in Cholangiocytes, Ca2+ Agonists in Bile Duct Cells, Effects of Ca2+ on Cholangiocyte Secretion, 11. Bile Acid Interactions with Cholangiocytes, Overview, Cholangiocyte Bile Acid Uptake, Intracellular Bile Acid Movement in Cholangiocytes, Bile Acid Efflux in Cholangiocytes, Cholehepatic Shunting of Bile Acids, Overview of the Regulation of ASBT Expression in Cholangiocytes, Bile Acid Signaling in Cholangiocytes, Bile Acid Synthesis and Conjugation in Cholangiocytes, Gallbladder Epithelial Cells, Bile Acid Effects on Cholangiocyte Function or Dysfunction in Humans, 12. Aquaporin-Mediated Water Transport in Intrahepatic Bile Duct Epithelial Cells, Molecular Biology of Mammalian AQPs, AQPs in Cholangiocytes, 13. ABC Transporters, Organic Solute Carriers and Drug Metabolising Enzymes in Bile Duct Epithelial Cells, Transporters in Hepatocytes, Transporters and Drug Metabolizing Enzymes in Cholangiocytes, Cholehepatic Shunt, Gallstones, 14. Regulation of Secretion in Human Gallbladder Epithelial Cells, Regulation of Mucin Secretion in the Gallbladder, Regulation of Fluid and Ion Transport in the Gallbladder, Bile Salt Transport and Regulating Functions in the Gallbladder Epithelium, 15. Ductal Bicarbonate Secretion in Human Cholestatic Liver Diseases, Biliary Transport of HCO3−/H+, ltered Biliary Transport of HCO3−/H+ in Primary Biliary Cirrhosis, In Vivo Imaging of Ductal Bicarbonate Secretion in Health and Disease, 16. Participation of Cytokines and Growth Factors in Biliary Epithelial Proliferation and Mito-Inhibition during Ductular Reactions, Conceptual Approach to Hepatic Responses to Injury 167, Ductular Reactions, Factors That Stimulate Biliary Epithelial Cell Proliferation in Vitro and Correlation with Ductular Reactions in Vivo, The Effect of Growth Factors on BEC Growth, Mito-Inhibitors and Cell Cycle Regulation, Gene Transfer in Vivo, 17. Estrogen Regulation of Cholangiocyte Proliferation, Estrogens Modulate Cholangiocyte Proliferation: Experimental Evidences, Role of Endogenous Estrogens in the Modulation of Cholangiocyte Proliferation, Intracellular Signaling Pathways Activated by Estrogens in Cholangiocytes, 18. Nerve Regulation of Cholangiocyte Functions, Anatomical and Morphological Features of the Biliary Epithelium, Experimental in Vivo and in Vitro Models for Studying the Role of Nerves in the Regulation of Cholangiocyte Functions, Brief Overview of Cholangiocyte Functions, Innervation of the Liver, Cholinergic Regulation of Cholangiocyte Functions, Adrenergic and Dopaminergic Regulation of Cholangiocyte Functions, 19 Cholestasis and Fibrogenesis, Liver Fibrosis: Definition and General Mechanisms, Cholestasis and Fibrogenesis: A Common Association, Cholangiopathies As Chronic Fibrogenic Disorders, Liver Fibrosis Associated with Bile Duct Damage/Ductopenia: Primary Biliary Cirrhosis As a Paradigm of Inflammatory Cholangiopathy, Liver Fibrosis Associated with Bile Duct Proliferation, 20. Apoptosis of Biliary Epithelial Cells, Molecular Regulation of Apoptosis in the Bile Duct Epithelial Cells, Regulators of Apoptosis in the Biliary Epithelium, Dysregulation of Apoptosis in Biliary Carcinogenesis, 21. Cytokine Regulation of Cholangiocyte Growth, Cytokines and Biliary Epithelia, Cytokine Mediated Growth Regulation in Pathophysiological Processes, Biliary Tract Inflammation, Cytokine Regulation of Biliary Epithelial Proliferation, 22. Fas-Mediated Cholangiopathy in a Murine Model of Graft-versus-Host Disease, Fas Receptor Is Expressed by Cholangiocyte in Situ and in Vitro, Alloreactive Lymphocytes Are Cytotoxic to Cultured Cholangiocytes, 23. Functional Heterogeneity of the Intrahepatic Biliary Epithelium, Overview of Biliary Anatomy and Morphology, Cholangiocyte Functions, In Vivo and in Vitro Experimental Models, Functional Heterogeneity Found in Other Epithelia, Heterogeneity of Cholangiocytes, Proliferative Heterogeneity and Apoptotic Susceptibility of Small and Large Cholangiocytes in Response to Injury and Toxins, 24. In Vitro Systems for the Study of the Intrahepatic Biliary Epithelium, Source of Intrahepatic Biliary Epithelial Cells for in Vitro Studies, Maintenance of Intrahepatic Biliary Epithelial Cells in Vitro, Other Potential Models for Culture of Intrahepatic Biliary Epithelial Cells, 25. Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease 268  Smads Sox17 Foxa Proteins, Hex Proxl Cell-Cell Interactions and ECM Remodeling, Hepatic Growth Signals from the Cardiac Mesoderm, FGF Bmp Signaling and Hepatic Induction, ELF Smad Signaling in Liver and Biliary Tree Development, Smad2/3 Hlx HGF c-Met and TGF-beta, Apoptosis Necrosis and Generation of Tissue Architecture, Coordination with Vascular Development, Division of Hepatocyte and Biliary Lineages, Extrahepatic Bile Ducts and the Gall Bladder Formation, Fetal Liver Cell Lines to Study the Hepatic-Biliary Split, Hepatocyte Differentiation after Hematopoiesis, HNF4 Control of Hepatocyte Differentiation, Genetic Defects in Hepatobiliary Transport, Alagille Syndrome and Jagged 1, ATP8B1 ABCB11 ABCB4 Deficiency, 26. Drug-Induced Vanishing Bile Duct Syndromes, Drug-Induced Vanishing Bile Duct Syndrome, Histopathological Features, Toxin-Induced Bile Duct Injury, Iatrogenic Sclerosing Cholangitis, 27. Biliary Atresia, History, Embryology/Morphogenesis, Clinical Manifestations, Natural History, Diagnosis, Treatment, Pathogenesis, 28. Primary Biliary Cirrhosis Bench to Bedside, Clinical Feature