Extracellular Matrix and The Liver (eBook)

Cover 1
Extracellular Matrix and the Liver 4
Copyright Page 5
Contents 6
Contributors 16
Preface 22
PART I: Basic Science of Extracellular Matrix 24
Chapter 1. New Insights into the Extracellular Matrix 26
I. Introduction 26
II. Biochemistry of Extracellular Matrix 27
III. Current Topics in Extracellular Matrix Research 33
IV. Extracellular Matrix in Liver Cirrhosis Compared with That in Normal Liver 38
References 40
Chapter 2. Dynamic Regulation of Basement Membrane Collagen IV Gene Expression in Malignant Tumors 46
I. Introduction 47
II. Tissue-Specific Expression of Collagen IV Genes 48
III. Supramolecular Aggregates of Collagen IV 50
IV. Why Are Basement Membranes Important for Diagnosis in Surgical Pathology? 53
V. Differential Expressions of the Six a(IV) Chains in Mammary Neoplasia 53
VI. Protective Effects of Basement Membranes Against Cancer Invasion Due to Reorganization of a(IV) Chains 56
VII. Conclusion 58
References 59
Chapter 3. Regulation of Phenotypes of Human Aorta Endothelial Cells and Smooth Muscle Cells in Culture by Type IV Collagen Aggregates 62
I. Introduction 62
II. Human Aortic Smooth Muscle Cells on Type IV Collagen Gel 64
III. Physical Property-Determining Effects of Type IV collagen aggregates 67
IV. Perspectives 74
V. Conclusion 76
References 76
Chapter 4. Functions of Proteoglycan/Glycosaminoglycan in Liver 78
I. Introduction 78
II. Chondroitin Sulfate/Dermatan Sulfate Proteoglycans in Liver Reticulin Fiber 83
III. Hyaluronan as a Diagnostic Marker for Liver Cirrhosis 90
References 94
Chapter 5. SPARC, a Matricellular Protein That Regulates Cell–Matrix Interaction: Implications for Vascular and Connective Tissue Biology 98
I. Introduction 99
II. Matricellular Proteins 99
III. SPARC-Null Mice 103
IV. Perspectives 106
References 107
PART II: Cells Responsible for Extracellular Matrix Production 110
Chapter 6. Cells Responsible for Extracellular Matrix Production in the Liver 112
I. Introduction 112
II. Microenvironment in the Normal Liver 112
III. Liver Injury and Changes in Microenvironment 114
IV. Conclusion 124
References 124
Chapter 7. Different Hepatic Cell Populations of the Fibroblast Lineage with Fibrogenic Potential 128
I. Introduction 129
II. Approaches for the Identification and Further Characterization of the Different Hepatic Cell Populations with Fibrogenic Potential 133
III. Expression of Extracellular Matrix Proteins, Proteases, and Protease Inhibitors by HSC and rMF 138
IV. Expression of Cytokines and Cell Membrane Receptors by HSC and rMF 139
V. Fibulin-2: A Novel Marker for the Differentiation of HSC and Rat Liver Myofibroblasts 140
VI. Distribution of HSC and rMF in Rat Liver Tissue 142
VII. HSC as a Model System to Study the Role of Cells of the Fibroblast Lineage during Tissue Repair 149
VIII. Outlook 152
References 153
Chapter 8. Role of Sinusoidal Endothelial Cells in Liver Inflammation and Repair 158
I. Introduction 159
II. Intercellular Adhesion Molecule-1 Upregulation on Sinusoidal Endothelial Cells Precedes Infiltration with Inflammatory Cells and Development of Necrotic Areas 160
III. Tumor Necrosis Factor-a Enhances Intercellular Adhesion Molecule-1 Transcript Level in Culture of Sinusoidal Endothelial Cells 162
IV. Transmigration 165
V. Regeneration and Scar Formation 168
References 172
PART III: Activation Mechanism of Hepatic Stellate Cells and Signal Transduction 176
Chapter 9. Molecular Mechanism of Stellate Cell Activation and Extracellular Matrix Remodeling 178
I. Introduction 178
II. Molecular Mechanism of Stellate Cell Activation and Extracellular Matrix Remodeling 186
III. Conclusions and Future Prospects 191
References 192
Chapter 10. Peroxisome Proliferator-Activated Receptor . and Hepatic Stellate Cell Activation 202
I. Deficiency of RXR and 9-cis RA in Activated Hepatic Stellate Cells 202
II. PPAR and HSC 203
III. PPAR. Is Reduced in Activated HSC 205
IV. PPAR. Ligands Suppress Activation of HSC 208
V. PPAR. Ligands and Collagen Gene Expression 208
VI. Remaining Questions Concerning PPAR. Dependence of Antifibrogenic Effects of TZD 209
References 210
Chapter 11. Role of Histone Deacetylases in Transcriptional Control of the Hepatic Stellate Cell Phenotype 212
I. Introduction 213
II. Effect of TSA on Hepatic Stellate Cells 217
III. Discussion 221
References 223
Chapter 12. Profibrogenic Actions of Hepatic Stellate Cells: Major Intracellular Signaling Pathways 230
I. Introduction 231
II. Polypeptide Growth Factor Receptors 232
III. Transforming Growth Factor-ß Receptor Superfamily 235
IV. Seven Transmembrane Domain Receptors 239
V. Tumor Necrosis Factor Receptor Superfamily 243
VI. Other Cytokine Receptors 245
VII. Cooperation between Growth Factor Receptor and Integrin Signaling 246
References 247
Chapter 13. Transcriptional Activation of Type I Collagen Gene during Hepatic Fibrogenesis 256
I. Introduction 257
II. COL1A2 Transcription in Skin Fibroblasts 257
III. COL1A2 Transcription in Hepatic Stellate Cells 259
IV. Smad Proteins Regulating COL1A2 Transcription in Activated Hepatic Stellate Cells 260
V. Cell Type-Specific Activation of COL1A2 Promoter during Hepatic Fibrogenesis in Vivo 264
VI. Molecular Mechanisms Responsible for Cell Type-Specific Activation of COL1A2 Promoter 266
VII. Conclusion 269
References 270
PART IV: Basic Science of Matrix Metalloproteinases and Tissue Inhibitor Metalloproteinases 272
Chapter 14. Advances in Matrix Metalloproteinases (MMPs), Membrane-Type MMPs, and a Disintegrin and Metalloproteinase and Their Roles in Cellular Interaction and Migration 274
I. Introduction 274
II. Soluble and Membrane-Type MMPs and Their Activation 276
III. ADAMs and ADAMTSs 280
IV. MMP Induction by Cell–Cell Interaction: A Role for Emmprin 284
V. Role of Metalloproteinases in Cell Migration 286
VI. Conclusions 292
References 292
Chapter 15. Transcriptional Regulation of Matrix Metalloproteinases 300
I. Introduction 300
II. Regulation of MMP Transcription 302
III. Single Nucleotide Polymorphisms in MMP Promoters 306
IV. Biology of MMP Gene Expression 309
V. MMPs as Therapeutic Targets 312
VI. Conclusion 314
References 315
Chapter 16. Knockout Mice of Matrix Metalloproteinase Genes 322
I. Introduction 322
II. Targeted Disruption of MMP Genes in Mice 323
III. Postnatal Development of Knockout Mice of MMPs 324
IV. MMP Knockout Mice and Disease 325
V. Conclusion 329
References 329
Chapter 17. Structures and Functions of Tissue Inhibitors of Metalloproteinases 332
I. Introduction 333
II. General Aspects of the TIMP Family 333
III. Multiple Functions of TIMPs 339
IV. Conclusions and Future Perspectives 345
References 346
PART V: Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Liver Fibrosis 354
Chapter 18. Gene Expression of Matrix Metalloproteinases in Acute and Chronic Liver Injuries 356
I. Introduction 356
II. Acute Liver Injury 357
III. Regeneration after Partial Hepatectomy 360
IV. Chronic CCL4 Liver Injury 362
V. Localization of MMP-2 and MMP-14 in Human Liver 363
VI. Regulation of MMPs 366
VII. Conclusions 367
References 367
Chapter 19. Role of Tissue Inhibitors of Metalloproteinases (TIMPs) in the Progression and Regression of Liver Fibrosis: Regulation of TIMP-1 Gene Expression in Hepatic Stellate Cells 370
I. Tissue Inhibitors of Metalloproteinases 371
II. TIMP Expression in Cultured Hepatic Stellate Cells 372
III. TIMP Expression by Hepatocytes and Kupffer Cells 374
IV. Role of TIMPs in the Progression of Liver Fibrosis 374
V. Role of TIMPs in the Regression of Liver Fibrosis 376
VI. Regulation of TIMP-1 Gene Expression in Activated Hepatic Stellate Cells 378
VII. Conclusions 379
References 380
Chapter 20. Stem Cells Expressing Matrix Metalloproteinase-13 mRNA Appear during Regression Reversal of Hepatic Cirrhosis 384
I. Reversibility of Hepatic Fibrosis 385
II. Experimental Model 386
III. Collagenase in Recovery from Liver Cirrhosis 389
IV. Gene Expression of MMPs and TIMPs in Recovery from Liver Cirrhosis 390
V. Stem Cells Expressing MMP-13 in Recovery from Liver Cirrhosis 399
VI. Hypothesis and Proposal of a New Strategy for the Treatment of Liver Cirrhosis 401
VII. Conclusion 405
References 405
PART VI: New Strategies for the Treatment of Liver Cirrhosis 412
Chapter 21. Retinoids in Liver Fibrosis: Induction of Proteolytic Activation of Transforming Growth Factor-ß by Retinoic Acid and Its Therapeutic Control by Protease Inhibitors 414
I. Introduction 415
II. Retinoic Acid and Liver Fibrosis 416
III. Protease Inhibitors 419
IV. Conclusions 423
References 424
Chapter 22. Role of Growth Hormone Resistance and Impaired Insulin-like Growth Factor-I Bioavailability in the Pathogenesis of Cirrhosis and Its Complications 428
I. Liver and the GH:IGF:IGFBP Axis 429
II. The State of Acquired Growth Hormone Resistance 432
III. The GH:IGF:IGFBP Axis in the Pathogenesis of Cirrhosis 432
IV. GH:IGF:IGFBP Pathophysiology and Cirrhosis Complications 441
V. Growth Hormone and IGF-I as Therapy in Cirrhosis 444
References 448
Chapter 23. Resolution of Liver Fibrosis in Hepatitis C Patients by Interferon Therapy and Prevention of Hepatocellular Carcinoma 454
I. Introduction 454
II. Stepwise Progression of Hepatic Fibrosis Toward HCC 455
III. Interferon Treatment and Its Response 457
IV. Histological Response 457
V. Histological Evaluation 458
VI. Natural Course of Fibrosis Progression 458
VII. Long-term Effect of IFN on Histological Improvement 459
VIII. Improvement of Hepatic Fibrosis and Inhibition of Hepatocarcinogenesis by Interferon Therapy Study 460
IX. Conclusion 462
References 463
Chapter 24. Possible Gene Therapy for Liver Cirrhosis 466
I. Introduction 466
II. Liver Fibrosis/Liver Cirrhosis 467
III. Hepatocyte Growth Factor Gene Therapy 468
References 476
Index 478