Front Cover

Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Target Tissues and Therapy

Copyright

Contents

Contributors

Preface

Chapter One: The Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs

1. Introduction

2. Lung Development

2.1. MMPs in Branching Morphogenesis

2.2. MMPs in Lung Angiogenesis

2.3. MMPs in Lung Alveolarization

3. MMPs in Lung Repair Responses to Injury

4. MMPs in Destruction of the Lung

4.1. Lung Diseases Affecting the Airways

4.1.1. MMPs in COPD and Emphysema

4.1.2. MMPs in Asthma

4.1.3. MMPs in CF

4.2. Lung Diseases Affecting the Alveoli

4.2.1. MMPs in Pneumonia

4.2.2. MMPs in Adult Respiratory Distress Syndrome

4.2.3. MMPs in Bronchopulmonary Dysplasia

4.3. Lung Diseases Affecting the Interstitia

4.3.1. MMPs in Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis

5. Concluding Remarks

References

Chapter Two: Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target

1. Introduction

2. Matrix Metalloproteinases

3. Renal MMPs/TIMPs

4. MMPs in Acute Kidney Injury

5. MMPs in Chronic Kidney Disease

5.1. Glomerulosclerosis/Tubulointerstitial Fibrosis

5.2. Diabetic Nephropathy

5.3. Chronic Allograft Nephropathy

5.4. Polycystic Kidney Disease

5.5. Renal Carcinoma

6. MMPs and TIMPs: Biomarkers of Renal Disease

7. MMPs: Inflammation

8. Summary

References

Chapter Three: Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy

1. Diabetic Retinopathy

2. Matrix Metalloproteinases

3. Role of MMPs in Diabetic Retinopathy

3.1. Blood-Retinal Barrier

3.2. Inflammation

3.3. Neovascularization

3.4. Mitochondrial Damage and Apoptosis

4. Regulation of MMPs in Diabetic Retinopathy

4.1. Functional Regulation

4.2. Transcription Factors

4.3. Epigenetic Modifications

5. MMP Inhibitors: Promising Treatment Approaches

Acknowledgments

References

Chapter Four: Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

1. Introduction

2. Vascular and Placental MMPs During Pregnancy

3. Uteroplacental and Vascular Changes in Preeclampsia

4. Risk Factors in Preeclampsia

5. Abnormal Placentation and Placental Ischemia in Preeclampsia

5.1. Immune Responses and Inadequate Placentation in Preeclampsia

5.2. Integrins and Reduced Trophoblast Invasion and Spiral Artery Remodeling

5.3. MMPs, Abnormal Placentation, and Placental Ischemia

6. Circulating Bioactive Factors and MMPs in Preeclampsia

6.1. Proangiogenic and Antiangiogenic Factors in Preeclampsia

6.1.1. Vascular Endothelial Growth Factor

6.1.2. Placental Growth Factor

6.1.3. Soluble fms-Like Tyrosine Kinase-1

6.1.4. Soluble Endoglin

6.2. Cytokines, TNF-α, and Interleukins

6.3. Hypoxia-Inducible Factor

6.4. Reactive Oxygen Species

6.5. AngII and AT1 Receptor Agonistic Autoantibodies

7. MMPs and Vascular Dysfunction in Hypertensive Pregnancy and Preeclampsia

7.1. MMPs and ECM Abnormalities in Preeclampsia

7.2. MMPs and Endothelial Dysfunction in Preeclampsia

7.2.1. Changes in NO in Preeclampsia

7.2.2. MMPs and EDHF

7.2.3. MMPs and ET-1 in Preeclampsia

7.3. MMPs and Smooth Muscle Dysfunction in Preeclampsia

7.3.1. VSM Ca2+ in Preeclampsia

7.3.2. PKC, MAPK, and Rho-Kinase in Preeclampsia

8. MMPs and Uterine Contraction During Pregnancy and Labor

8.1. Uterine Stretch, Sex Hormones, and MMPs During Pregnancy

8.2. Uterine MMP Inducers and EMMPRIN During Pregnancy

8.3. MMPs, Uterine ECM, and Uterine Relaxation Mechanisms

9. Dysregulation of Uterine MMPs During Preterm Labor

10. MMPs in Prediction and Management of Complications of Pregnancy

11. Concluding Remarks

Acknowledgments

Conflict of Interest

References

Chapter Five: Matrix Metalloproteinases, Neural Extracellular Matrix, and Central Nervous System Pathology

1. Neural Extracellular Matrix Structure

2. nECM Modifiers

3. Cerebrovascular Diseases

4. Alzheimer's Disease and Aging

5. Epilepsy

6. Multiple Sclerosis

7. CNS Cancer

8. Peripheral Nerve Injury

9. Targeted Therapy of nECM

10. Concluding Remarks

Acknowledgments

References

Chapter Six: Matrix Metalloproteinases in Bone Resorption, Remodeling, and Repair

1. Introduction

2. Overview of the General Properties of Matrix Metalloproteinases (MMPs) and Their Inhibitors (TIMPs and RECK)

3. Bone Cells and ECM

3.1. Osteoblasts and Osteocytes

3.2. Bone ECM

3.3. Osteoclasts

4. Bone Modeling, Remodeling, and Resorption

5. Bone Loss Associated to Abnormal Bone Remodeling

5.1. Bone Loss Due to Osteoporosis

5.2. Bone Loss Induced by Bone Metastasis

6. Bone Repair/Regeneration

7. Perspectives on Bone Bioengineering

Acknowledgments

References

Chapter Seven: Matrix Metalloproteinases and Synovial Joint Pathology

1. Introduction

2. Structure and Function(s) of MMPs

2.1. MMP-1

2.2. MMP-2

2.3. MMP-3

2.4. MMP-7

2.5. MMP-8

2.6. MMP-9

2.7. MMP-13

2.8. MT-MMP

3. MMPs and RA

4. MMPs and OA

5. MMPs and PsA

6. MMPs and Spondyloarthropathies

7. Three Mechanisms Regulating MMPs: Dysfunction in Synovial Joint Pathologies?

7.1. Tissue Inhibitor of Metalloproteinases

7.2. MMP-9/NGAL Complex

7.3. Signal Transduction Pathways

8. Conclusions and Future Perspective

Acknowledgments

References

Chapter Eight: Metalloproteinases in Rheumatoid Arthritis: Potential Therapeutic Targets to Improve Current Therapies

1. Introduction

2. Metalloproteinases

3. Role of MPs in RA Pathology

3.1. Inflammation

3.2. Destruction of Joint Tissue

4. Pathways to Improve Current RA Therapy

4.1. Combination Therapy

4.2. Failure of Broad-Spectrum MP Inhibitors

4.3. Therapeutic Potential of Highly Selective Anti-MP Therapy

5. Conclusion

Acknowledgment

References

Chapter Nine: The Roles of Matrix Metalloproteinases in Pancreatic Cancer

1. Introduction

2. Initial Implication of MMPs in Pancreatic Cancer

3. Pancreatic Cancer Clinical Trials Using MMP Inhibitors

4. Roles of Specific MMPs in Pancreatic Cancer

5. Development of MT1-MMP Inhibitors

6. Concluding Remarks

Acknowledgments

References

Chapter Ten: Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeli ...

1. Introduction

2. MMP-Substrate Interaction

3. Regulation of MMP Expression/Activity

4. Tissue Inhibitors of Metalloproteinases

5. Other Biological and Pleiotropic Inhibitors of MMPS

6. Synthetic MMP Inhibitors

6.1. Derivatives of Early ZBGs

6.2. Nitrogen-Based ZBGs

6.3. Heterocyclic Bidentate ZBGS

6.4. Tetracycline-Based MMP Inhibitors

6.5. Nonzinc-Binding MMP Inhibitors

6.6. Mechanism-Based MMP Inhibitors

7. MMP Inhibitors as Investigational Tools in Biological Processes

7.1. MMP Inhibitors and Role of MMPs in Smooth Muscle Relaxation

7.2. MMP Inhibitors and Role of MMPs in Smooth Muscle Migration

7.3. MMP Inhibitors and Role of MMPs in Smooth Muscle Proliferation

7.4. MMP Inhibitors and Role of MMPs in Angiogenesis

7.5. MMP Inhibitors and Role of MMPs in Cell Apoptosis

8. MMP Inhibitors as Potential Tools in Pathological Conditions

8.1. MMP Inhibitors and Role of MMPs in Hypertension

8.2. MMP Inhibitors and Role of MMPs in Atherosclerosis

8.3. MMP Inhibitors and Role of MMPs in Aneurysm

9. Concluding Remarks

Acknowledgments

Conflict of Interest

References

Index

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