List of Contributors

xiii

Preface

xxiii

Acknowledgements

xxiv

PART ONE

INTRODUCTION

1

1

Organizational Principles of the Liver   Joe W. Grisham

3

2

Embryonic Development of the Liver   Roque Bort and Kenneth S. Zaret

17

PART TWO

THE CELLS

27

3

Microtubules, Actin Filaments and Motor-Mediated Vesicular Transport   Ronald R. Marchelletta and Sarah F. Hamm-Alvarez

29

4

Molecular Motors   Peter Satir

45

5

Ion Pumps and Molecular Motors: P-, F-, and V-Type Atpases   Sarah Bond, Daniel J. Cipriano, and Michael Forgac

57

6

Hepatocyte Surface Polarity: its Dynamic Maintenance and Establishment   Lelita T. Braiterman and Ann L. Hubbard

73

7

Endocytosis as an Essential Process in Liver Function and Pathology   Barbara Schroeder and Mark Mcniven

107

8

Membrane Transport in Hepatocellular Secretion   Susan Chi and Mark Mcniven

125

9

Mitochondria   Kasturi Mitra

137

10

Nuclear Pore Complex   Joseph S. Glavy

147

11

Protein Maturation and Processing at the Endoplasmic Rcticulutn   Ramanujan S. Hegde

157

12

Protein Degradation and the Lysosomal System   Susmita Kaushik and Ana Maria Cuervo

173

13

Peroxisome Assembly, Degradation, and Disease   Peter K. Kim

191

14

Gap and Tight Junctions in Liver: Composition, Regulation, and Function   Takashi Kojima, Norimasa Sawada, Hiroshi Yamaguchi, Alfredo G. Fort, and David C. Spray

201

SECTION A

HEPATOCYTE

221

15

Copper Metabolism and the Liver   Michael L. Schilsky and Dennis J. Thiele

223

16

The Central Role of the Liver in Iron Storage and Regulation of Systemic Iron Homeostasis   Tracey A. Rouault, Victor Gordeuk, and Gregory Anderson

235

17

Disorders of Bilirubin Metabolism   Namita Roy Chowdhury and Jayanta Roy Chowdhury

251

4.21

The Porphyries   Peter N. Meissner, Richard J. Hift, Ralph E. Kirsch

18

Hepatic Fatty Acid Metabolism and Dysfunction   David L. Silver

257

19

Lipoprotein Metabolism and Cholesterol Balance   David E. Cohen

271

SECTION B

BILE SECRETION

287

20

Bile Acids and the Enterohepatic Circulation   Alan F. Hofmann

289

21

Hepatocyte Basolateral Membrane Organic Anion Transporters   Jo H. Choi, John W. Murray, and Allan W. Wolkoff

305

22

Nuclear Receptors Regulate Bile Acid Synthesis   Guorong Xu and Gerald Salen

323

4.27

Hormonal Regulation of Bile Secretion   Francis R. Simon

4.28

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

339

24

Apical Recycling of Canalicular ABC Transporters   Yoshiyuki Wakabayashi and Irwin M. Arias

349

25

Cholangiocyte Functions in Health and Disease: the Ciliary Connection   Anatoliy I. Masyuk, Tatyana V. Masyuk, and Nicholas F. Larusso

359

SECTION C

SINUSOIDAL CELLS

371

26

The Hepatic Sinusoidal Endothelial Cell: Morphology, Function, and Pathobiology   Laurie D. Deleve

373

4.30

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

389

28

Hepatic Stellate Cells   Marcos Rojkind and Karina Reyes-Gordillo

407

29

Hepatic Fibrosis   Ramón Bataller and David A. Brenner

433

30

Matrix   Giuliano Ramadori and Jozsef Dudas

453

PART THREE

INTERRELATED CELL FUNCTIONS

469

31

Insulin Resistance   Varman T, Samuel, Kitt F. Petersen, and Gerald I. Shulman

471

32

Ca²⁺ Signaling in the Liver   Fatima M. Leite, Mateus T. Guerre, and Michael H. Nathanson

485

4.35

Synthesis of and Signalling through D-3 Phosphoinositides   Rial a Christensen, Isabel De Aos Scherpenseel, Lyuba Varticovski

4.39

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

511

4.18

Hypoxic, Ischemic and Reperfusion Injury to Liver   John J. Lemasters

4.19

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 Delia Fazia, and Paolo Sassone-Corsi

521

35

AMPK: Central Regulator of Glucose and Lipid Metabolism   Maria M. Mihaylova and Reuben J. Shaw

535

3.16

Energy Metabolism   Sam Seifter and Sasha Englard

36

Liver Regeneration   Nelson Fausto and Jean S. Campbell

549

4.40

Interleukin-6 Signaling during the Acute-Phase Response of the Liver   Johannes G. Bode, Peter C. Heinrich

4.43

Hepatocyte Growth Factor: its Role in Hepatic Growth and Pathobiology   Reza Zamegar, 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

567

4.5

Gene Regulation and in Vivo Function of Liver Transcription Factors   Robert H. Costa, Al-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

577

PART FOUR

RELATION TO OTHER ORGANS

597

39

Hepatic Encephalopathy   Roger F. Butterworth and Javier Vaquero

599

40

The Kidney in Liver Disease   Moshe Levi

619

41

Critical Role of the Liver in Coagulation   Robert Fathke, Ze Peng, Basil Golding, and Chava Kimchi-Sarfaty

639

PART FIVE

PATHOBIOLOGICAL ANALYSIS

659

42

Inheritable Cholesta He Disorders   Paul Gissen and A. S. Knisely

661

4.48

Alpha 1-Antitrypsin Deficiency   David H. Perlmutter

43

Adaptive Regulation of Hepatocyte Transporters in Cholestasis   James L. Boyer

681

44

Pathogenesis of Portal Hypertension   Roberto J. Groszmann and Juan G. Abraldes

703

45

Non-Alcoholic Fatty Liver Disease: a Pathophysiological Perspective   Michael Fuchs and Arun J. Sanyal

719

46

Pathophysiology of Alcoholic Liver Disease   Natalia Nieto and Marcos Rojkind

743

47

Inflammation and Drug-Induced Liver Injury   Robert A. Roth and Patricia E. Ganey

773

48

Hepatocyte Apoptosis   Cynthia R.L. Webster

783

49

Back to the Future: a Backward Glance at the Forward Progress of Hepatitis Virus Research   Harvey J. Alter

803

50

Molecular Biology of Hepatitis Viruses   Christoph Seeger, Michael M.C. Lai, and William S. Mason

807

51

Immune Mechanisms of Viral Clearance and Disease Pathogenesis during Viral Hepatitis   Carlo Ferrari and Mario Mondelli

835

4.41

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 W. Thomas London

859

53

Viral Escape Mechanisms in Hepatitis C and the Clinical Consequences of Persistent Infection   Stanley M. Lemon, Patrizia Farci, and Marc G. Ghany

877

54

Current and Future Therapy for Hepatitis B and C   Gary L. Davis and Jean-Michel Pawlotsky

899

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

921

PART SIX

HORIZONS

933

56

Tissue Engineering of the Liver   Gregory H. Underhill, Salman R. Khetani, Alice A. Chen, and Sangeeta N. Bhatia

935

57

Aging and the Uncertain Roles of Sirtuins   J. Fred Dice

955

58

The Liver Proteome   Laura Beretta

961

59

Liver-Directed Gene Therapy   Betsy T. Kren, Clifford J. Steer, Namita Roy Chowdhury, and Jayanta Roy Chowdhury

965

4.63

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

991

61

Genome-Wide Expression Profiling of Human Hepatocellular Carcinoma   Anuradha Budhu and Xin Wei Wang

999

62

Cell Cycle Control in the Liver   Jeffrey H. Albrecht and Lisa K. Mullany

1015

63

Mirnas and Liver Biology   Charles E. Rogler and Leslie E. Rogler

1029

64

Imaging Cellular Proteins and Structures: Smaller, Brighter, and Faster   Erik Snapp

1053

65

Zebraftsh as a Model System for the Study of Liver Development and Disease   Randolph P. Matthews

1067

66

The Hepatocyte and the Cancer Cell: Dr Jekyll and Mr Hyde   Jean-Pierre Gillet, Michael M. Gottesman, and Mitsunori Okabe

1075

67

The Role of Endocannabinoids and their Receptors in the Control of Hepatic Functions   George Kunos, Douglas Osei-Hyiaman, Sándor Batkai, Pál Pacher, Bin Gao, Won-II Jeong, Jie Liu, and Gregorz Godlewski

1091

68

Telomeres and Aging, Cancer, and Hepatic Fibrosis   Hans L. Tillmann, Ruben R. Plentz, Yvonne Begus-Nahrmann, André Lechel, and Lenhard K. Rudolph

1105

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

1121

70

The “Green Liver” and Transcriptional Regulation of Phase II Detoxification Genes   Christopher Johnson and Jonathan Arias

1131

Index

1139