The Liver

Editor: Irwin Arias, MD, National Institutes of Health, Bethesda, Maryland. Professor of Physiology, Emeritus, Tufts University School of Medicine, Boston, Mass. Visiting Professor of Medicine, Albert Einstein College of Medicine, Bronx, NY. Associate editors: James L. Boyer, Yale University School of Medicine, New Haven, CT, USA David Shafritz, Albert Einstein College of Medicine, Bronx, NY, USA Nelson Fausto, Professor and Chair, Department of Pathology, University of Washington, Seattle, WA, USA. Harvey Alter, Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA David E. Cohen,.Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA Allan Wolkoff, Albert Einstein College of Medicine, Bronx, NY, USA

List of Contributors Preface Acknowledgements PART ONE INTRODUCTION 1 Organizational Principles of the Liver Joe W. Grisham 2 Embryonic Development of the Liver Roque Bort and Kenneth S. Zaret PART TWO THE CELLS 3 Microtubules, Actin Filaments and Motor-mediated Vesicular Transport Ronald R. Marchelletta and Sarah F. Hamm-Alvarez 4 Molecular Motors Peter Satir 5 Ion Pumps and Molecular Motors: P-, F-, and V-type ATPases Sarah Bond, Daniel J. Cipriano, and Michael Forgac 6 Hepatocyte Surface Polarity: Its Dynamic Maintenance and Establishment Lelita T. Braiterman and Ann L. Hubbard 7 Endocytosis as an Essential Process in Liver Function and Pathology Barbara Schroeder and Mark McNiven 8 Membrane Transport in Hepatocellular Secretion Susan Chi and Mark McNiven 9 Mitochondria Kastuei Mitra 10 Nuclear Pore Complex Joseph S. Glavy 11 Protein Maturation and Processing at the Endoplasmic Reticulum Ramanujan S. Hegde 12 Protein Degradation and the Lysosomal System Susmita Kaushik and Ana Maria Cuervo 13 Peroxisome Assembly, Degradation, and Disease Peter K. Kim 14 Gap and Tight Junctions in Liver: Composition, Regulation, and Function Takashi Kojima, Norimasa Sawada, Hiroshi Yamaguchi, Alfredo G. Fort, and David C. Spray SECTION A HEPATOCYTE 15 Copper Metabolism and the Liver Michael L. Schilsky and Dennis J. Thiele 16 The Central Role of the Liver in Iron Storage and Regulation of Systemic Iron Homeostasis Tracey A. Rouault, Victor Gordeuk, and Gregory Anderson 17 Disorders of Bilirubin Metabolism Namita Roy Chowdhury and Jayanta Roy Chowdhury GH4.21. The porphyrias Peter N. Meissner, Richard J. Hift, Ralph E. Kirsch 18 Hepatic fatty acid metabolism and dysfunction David L. Silver 19 Lipoprotein Metabolism and Cholesterol Balance David E. Cohen SECTION B BILE SECRETION 20 Bile Acids and the Enterohepatic Circulation Alan F. Hofmann 21 Hepatocyte Basolateral Membrane Organic Anion Transporters Jo. H. Choi, John W. Murray, and Allan W. Wolkoff 22 Nuclear Receptors Regulate Bile Acid Synthesis Guorong Xu and Gerald Salen GH4.27. Hormonal regulation of bile secretion Francis R. Simon GH4.28. Nucleotide transport and regulation of bile formation Richard M. Roman and J. Gregory Fitz 23 The Function of the Canalicular Membrane in Bile Formation and Secretion Ronald P.J. Oude Elferink and Coen C. Paulusma 24 Apical Recycling of Canalicular ABC Transporters Yoshiyuki Wakabayashi and Irwin M. Arias 25 Cholangiocyte Functions in Health and Disease: The Ciliary Connection Anatoliy I. Masyuk, Tatyana V. Masyuk, and Nicholas F. LaRusso SECTION C SINUSOIDAL CELLS 26 The Hepatic Sinusoidal Endothelial Cell: Morphology, Function, and Pathobiology Laurie D. DeLeve GH4.30. Endothelial and pit cells Filip Braet, Dianzhong Luo, Ilan Spector, David Vermijlen, Eddie Wisse 27 Fenestrations in the Liver Sinusoidal Endothelial Cell Victoria C. Cogger and David G. Le Couteur 28 Hepatic Stellate Cells Marcos Rojkind and Karina Reyes-Gordillo 29 Hepatic Fibrosis Ram'on Bataller and David A. Brenner 30 Matrix Giuliano Ramadori and Jozsef Dudas PART THREE INTERRELATED CELL FUNCTIONS 31 Insulin Resistance Gerald I. Shulman and Varman Samuel 32 Ca2+ Signaling in the Liver M. Fatima Leite, Mateus T. Guerra, and Michael H. Nathanson GH4.35 Synthesis of and signalling through D-3 phosphoinositides Rial A Christensen, Isabel De Aos Scherpenseel, Lyuba Varticovski GH4.39. Nitric oxide in the liver Mark G. Clemens 33 Role of Intracellular Iron Movement and Oxidant Stress in Hepatocellular Injury John J. Lemasters, Akira Uchiyama, Jae-Sung Kim, Kazuyoshi Kon, and Hartmut Jaeschke GH4.18. Hypoxic, Ischemic and reperfusion injury to liver John J. Lemasters GH4.19. Protective mechanisms against reactive oxygen species Masayasu Inoue 34 Regulatory Pathways of Liver Gene Expression: The Central Role of Cyclic AMP Giuseppe Servillo, Maria Agnese Della Fazia, and Paolo Sassone-Corsi 35 AMPK: Central Regulator of Glucose and Lipid Metabolism Maria M. Mihaylova and Reuben J. Shaw GH3.16. Energy Metabolism Sam Seifter and Sasha Englard 36 Liver Regeneration Nelson Fausto GH4.40. Interleukin-6 signaling during the acute-phase response of the liver Johannes G. Bode, Peter C. Heinrich GH4.43. Hepatocyte growth factor: its role in hepatic growth and pathobiology Reza Zarnegar, Marie C. Defrances, George K. Michalopoulos 37 Ribosome Biogenesis and its Role in Cell Growth and Proliferation in the Liver Stefano Fumagalli and George Thomas GH4.5. Gene regulation and in vivo function of liver transcription factors Robert H. Costa, AI-Xuan Le Holternan, Francisco M. Rausa, Guy R. Adami 38 Liver Repopulation by Cell Transplantation and the Role of Stem Cells David A. Shafritz, Michael Oertel, Mariana D. Dabeva, and Markus Grompe PART FOUR RELATION TO OTHER ORGANS 39 Hepatic Encephalopathy Roger F. Butterworth and Javier Vaquero 40 The Kidney in Liver Disease Moshe Levi 41 Critical Role of the Liver in Coagulation Robert Fathke, Ze Peng, Basil Golding, and Chava Kimchi-Sarfaty PART FIVE PATHOBIOLOGICAL ANALYSIS 42 Inheritable Cholestatic Disorders Paul Gissen and Alex S. Knisely GH4.48. Alpha 1-Antitrypsin deficiency David H. Perlmutter 43 Adaptive Regulation of Hepatocyte Transporters in Cholestasis James L. Boyer 44 Pathogenesis of Portal Hypertension Roberto J. Groszmann and Juan G. Abraldes 45 Non-alcoholic Fatty Liver Disease: A Pathophysiological Perspective Michael Fuchs and Arun J. Sanyal 46 Pathophysiology of Alcoholic Liver Disease Natalia Nieto and Marcos Rojkind 47 Inflammation and Drug-induced Liver Injury Robert A. Roth and Patricia E. Ganey 48 Hepatocyte Apoptosis Cynthia R.L. Webster 49 Back to the Future: A Backward Glance at the Forward Progress of Hepatitis Virus Research Harvey J. Alter 50 Molecular Biology of Hepatitis Viruses Christoph Seeger, Michael M.C. Lai, and William S. Mason 51 Immune Mechanisms of Viral Clearance and Disease Pathogenesis During Viral Hepatitis Carlo Ferrari and Mario Mondelli GH4.41. Innate immune sensing and the toll-like receptors Bruce Beutler 52 Clinical Implications of the Molecular Biology of Hepatitis B Virus Timothy M. Block, Ju-Tao Guo, and Thomas W. London 53 Viral Escape Mechanisms in Hepatitis C and the Clinical Consequences of Persistent Infection Stanley M. Lemon, Patrizia Farci, and Marc G. Ghany 54 Current and Future Therapy for Hepatitis B and C Gary L. Davis and Jean-Michel Pawlotsky 55 Biological Principles and Clinical Issues Underlying Liver Transplantation for Virus-induced End-stage Liver Disease James R. Burton Jr, Hugo R. Rosen, and Paul Martin PART SIX HORIZONS 56 Tissue Engineering of the Liver Gregory H. Underhill, Salman R. Khetani, Alice A. Chen, and Sangeeta N. Bhatia 57 Aging and the Uncertain Roles of Sirtuins Fred J. Dice 58 The Liver Proteome Laura Beretta 59 Liver-directed Gene Therapy Betsy T. Kren, Clifford J. Steer, Namita Roy Chowdhury, and Jayanta Roy Chowdhury GH4.63. Novel strategies for manipulating hepatic gene expression in vivo Marxa L. Figueiredo, Eric P. Sandgren 60 Decoding the Liver Cancer Genome Ju-Seog Lee and Snorri S. Thorgeirsson 61 Genome-wide Expression Profiling of Human Hepatocellular Carcinoma Anuradha Budhu and Xin Wei Wang 62 Cell Cycle Control in the Liver Jeffrey H. Albrecht and Lisa K. Mullany 63 miRNAs and Liver Biology Charles E. Rogler and Leslie E. Rogler 64 Imaging Cellular Proteins and Structures: Smaller, Brighter, and Faster Erik Snapp 65 Zebrafish as a Model System for the Study of Liver Development and Disease Randolph P. Matthews 66 The Hepatocyte and the Cancer Cell: Dr Jekyll and Mr Hyde Jean-Pierre Gillet, Michael M. Gottesman, and Mitsunori Okabe 67 The Role of Endocannabinoids and Their Receptors in the Control of Hepatic Functions George Kunos, Douglas Osei-Hyiaman, S'andor B'atkai, P'al Pacher, Bin Gao, Won-Il Jeong, Jie Liu, and Gregorz Godlewski 68 Telomeres and Aging, Cancer, and Hepatic Fibrosis Hans L. Tillmann, Ruben R. Plentz, Yvonne Begus-Nahrmann, Andr'e Lechel, and Lenhard K. Rudolph 69 Treatment of Cirrhosis with Vitamin A-coupled Liposomes Carrying siRNA against Heat Shock Protein 47 Yoshiro Niitsu, Yasushi Sato, Kazuyuki Murase, and Junji Kato 70 The Green Liver and Transcriptional Regulation of Phase II Detoxification Genes Christopher Johnson and Jonathan Arias Index