Signaling Pathways in Liver Diseases E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1660

Veröffentlichungsjahr: 2015

Beschreibung

Signaling Pathways in Liver Diseases, Third Edition again provides hepatologists and hepatology researchers with an expert overview of the complex and novel cellular/extracellular signaling pathways in the liver, and their role in liver diseases. The last few years have seen a great number of developments in this field, which in turn have led to new opportunities for innovative treatments; however, the intricacy of these pathways and their interactions continue to provide a real challenge for clinicians. This outstanding book compiles the emerging knowledge into a single expert resource, cataloguing and organizing it into an accessible and understandable format.

With increased focus on the comprehension of cellular mechanisms involved in steatohepatitis, cirrhosis, and liver tumors, which has led to changes in the management of these diseases, this new edition also sees the introduction of exciting new chapters on key emerging areas such as:

• Autophagy
• Notch Pathway
• P13K/PTEN Signaling in Liver Diseases
• Sirtuins
• Hepcidin and Iron
• Epigenetic Regulation of Hepatic Stellate Cells and Liver Fibrosis
• Oxidative Stress and Signaling in the Liver.

Professors Dufour and Clavien have assembled an all-star cast of chapter authors, each of whom has provided clear and appropriate illustrations to reinforce the text, with a key points box offering a concise and handy summary. Self-assessment questions and answers allow the reader to test their own knowledge.

Signaling Pathways in Liver Disease, Third Edition is the perfect educational and reference tool to bridge the information exchange between the laboratory, the clinical ward, and the operating room, and an essential tool for the modern-day hepatologist.

Leseprobe

Table of Contents

Cover

Title page

List of Contributors

CHAPTER 1: Hepatocytes

Introduction

Liver and hepatocyte development

Phenotype and regeneration of the mature hepatocyte

Metabolic functions of the liver

References

CHAPTER 2: Signaling pathways in biliary epithelial cells

Introduction

Membrane receptors

Cyclic adenosine 3’, 5’-monophosphate (cAMP)

Cytosolic Ca

2+

Protein kinase C

Mitogen-activated protein kinase signaling

Phosphotidylinositol 3-kinase signaling

Notch signaling

Hedgehog signaling

Vascular endothelial growth factor

Pathological conditions

Conclusion

Acknowledgments

References

CHAPTER 3: Stellate cells

Polypeptide growth factor receptors

Transforming growth factor-β receptor superfamily

Seven transmembrane domain receptors

Chemokines

Tumor necrosis factor receptor superfamily

Nuclear receptor family

Other cytokine receptors

Adipokine receptors

Extracellular matrix signaling and hepatic stellate cells

Toll-like receptors

Cannabinoid receptors

Hedgehog pathway

Wnt pathway

Autophagy

Senescence of activated stellate cells

miRNAs and hepatic stellate cells

Conclusion

References

CHAPTER 4: Kupffer cells

Introduction

Markers, origin, and heterogeneity of Kupffer cells

M1 versus M2 polarization in Kupffer cells

Lipopolysaccharide signaling and endotoxin tolerance

Experimental approaches to deplete Kupffer cells

in vivo

Role of Kupffer cells in liver disease

Liver fibrosis and cirrhosis

Clinical applications and future perspectives

Acknowledgment

References

CHAPTER 5: Hepatic sinusoidal endothelial cells

Development and structure

Cellular functions

Pathobiology

Conclusion

References

CHAPTER 6: Extracellular matrix

Introduction

Components of the extracellular matrix in liver (Figure 6.1)

Changes in the extracellular matrix from normal to fibrotic liver

Pathways of cell–matrix interaction

The extracellular matrix and the stem cell niche

Metalloproteinases and their inhibitors

Conclusion

References

CHAPTER 7: Platelets: a new cell type in liver physiology

What are platelets?

Ischemia/reperfusion injury

Liver regeneration

Platelets in chronic liver disease

Conclusion

References

CHAPTER 8: Immune cell communication in liver disease and liver regeneration

Introduction

Adaptive immunity within the liver

Immune cell function in liver disease

References

CHAPTER 9: Extracellular vesicle RNA in liver disease

Introduction

Types of extracellular RNA

Classification of extracellular vesicles

Contents of extracellular vesicles

Assessment of extracellular vesicle RNA

Biological roles of extracellular vesicle RNA

Pathophysiological roles of extracellular vesicle RNA in liver disease

Translational implications

Conclusion

Acknowledgments

References

CHAPTER 10: Endoplasmic reticulum stress in nonalcoholic fatty liver disease

Endoplasmic reticulum

Unfolded protein response

Role of the unfolded protein response in liver physiology and physiopathology

Targeting the unfolded protein response to treat nonalcoholic fatty liver disease

References

CHAPTER 11: Autophagy

Introduction

Autophagy pathways and regulations

Autophagy and liver diseases

Conclusion

References

CHAPTER 12: CXC chemokine receptor signaling in liver repair and regeneration

Introduction

Mediators of liver regeneration

CXC chemokine ligands and receptors

Impact of CXC chemokines on liver repair and regeneration

Conclusion

References

CHAPTER 13: Metabolic regulation of liver regeneration

Introduction

Hepatic insufficiency-induced alterations in metabolism

Metabolic regulation of liver regeneration

A metabolic model of liver regeneration

Clinical implications

Conclusions

Acknowledgments

References

CHAPTER 14: TNF signaling

Introduction

TNF: molecules and structure

TNF signaling pathways

Function of TNF signaling in hepatic pathophysiology

Conclusion

Acknowledgments

References

CHAPTER 15: Fas/FasL

Introduction

Fas (CD95/APO-1) and Fas ligand (FasL/CD95L)

Fas/FasL apoptotic signaling

Fas/FasL noncytotoxic signaling

Fas/FasL in liver diseases

References

CHAPTER 16: Interferon signaling

Interferons

Induction of type I interferons

Interferon signaling through the Jak-STAT pathway

Effects of type I interferons

Interferon signaling in viral hepatitis

References

CHAPTER 17: Endocannabinoid signaling in liver pathologies

Endocannabinoids

The endocannabinoid system

The complex relationships of the endocannabinoid system

Signaling downstream of the CNRs

Nonalcoholic fatty liver disease

Alcoholic fatty liver

Progression to steatohepatitis

Liver fibrosis

Ischemia/reperfusion injury

Regeneration

Hepatitis C

Hepatocellular carcinoma

Conclusion

References

CHAPTER 18: The WNT/β-catenin pathway

Pathway and interactions

Wnt/β-catenin signaling in liver physiology

Wnt/β-catenin signaling in liver pathology

Therapeutic implications

References

CHAPTER 19: Hedgehog signaling in the liver

Introduction

Overview of the Hedgehog pathway

Hedgehog-producing and -responsive cells in the liver

Hedgehog in liver development and regeneration

Hedgehog in chronic liver disease

Hedgehog in liver cancer

Conclusion

Acknowledgments

References

CHAPTER 20: Notch pathway

Introduction

Notch signaling

Notch signaling in the liver

Notch signaling in liver diseases

Conclusion

References

CHAPTER 21: PI3K/PTEN signaling in liver diseases

Introduction

The PI3K signaling node in the liver

The Phosphatase and TENsin homolog on chromosome 10

PI3K/PTEN downstream signaling and function in the liver

Alterations of PI3K/PTEN signaling in hepatic diseases

Pharmaceutical targeting of the PI3K/PTEN signaling pathway

Summary

Acknowledgments

References

CHAPTER 22: mTOR signaling in liver disease

Introduction

mTOR signaling in hepatic metabolism

mTOR signaling in liver cancer

mTOR signaling in circadian rhythm

Conclusion

References

CHAPTER 23: LKB1/AMPK pathway in the control of hepatic energy metabolism

Introduction

Structure and regulation of AMPK

AMPK activation in liver

Regulation of glucose homeostasis

Regulation and management of lipid metabolism

Coordinated control of mitochondrial biogenesis and mitophagy

Regulation of protein synthesis and control of cell growth

Regulation of hepatocyte polarization and bile canicular network formation

Conclusions and perspectives

References

CHAPTER 24: NF-κB

Introduction

Signaling pathway for NF-κB activation

TNF-α-mediated NF-κB activation and liver injury

Ischemia-reperfusion (I/R) liver injury

Role of NF-κB in liver regeneration

NF-κB and liver fibrosis

Nonalcoholic fatty liver disease and NF-κB

IKK-NF-κB and hepatocarcinogenesis

Clinical applications and future perspectives

Acknowledgment

References

CHAPTER 25: c-Jun NH

2

-terminal kinases in liver diseases

Introduction

Functions and targets of JNKs in cell biology

JNKs in liver disease

Conclusion

References

CHAPTER 26: p53

Introduction

The transcription factor p53

Protein structure of p53

Regulation of p53 protein levels

Stress response: arrest of cell cycle and DNA repair

Stress response: apoptosis

Metabolic regulation by p53

p53 function in liver disease

References

CHAPTER 27: Sirtuins

Introduction

SIRT1

SIRT2

SIRT3

SIRT4

SIRT5

SIRT6

SIRT7

Conclusion

Acknowledgments

References

CHAPTER 28: Bile acids and their receptors

Introduction

Role of bile acid-activated nuclear receptors for bile acid metabolism, bile secretion, and cholestasis

Role of bile acid-activated nuclear receptors for lipid and glucose metabolism

G protein-coupled receptor for bile acids

Acknowledgments

References

CHAPTER 29: Hepcidin and iron

Introduction

Hepcidin synthesis and function

Hepcidin regulation

Stimulatory signals and signaling pathways

Inhibitory signals and pathways

Conclusion

References

CHAPTER 30: Gut microbiome and liver diseases

Introduction

Microbiota and nonalcoholic fatty liver disease

Microbiota and alcoholic liver disease

Microbiota and liver cirrhosis

Conclusion

References

CHAPTER 31: Epigenetic regulation of hepatic stellate cells and liver fibrosis

Introduction

What is epigenetics?

Developmental epigenetics

A basic overview of epigenetic mechanisms

The role of epigenetic mechanisms in hepatic stellate cells and liver fibrosis

Cross-talk between DNA methylation and histone modifications

Histone modifications

DNA methylation

MicroRNAs

Conclusion

References

CHAPTER 32: Signaling in hepatocellular carcinoma

Introduction

Mechanisms of pathway deregulation

Deregulated pathways in hepatocellular carcinoma

Pathway-based therapeutics in oncology

Molecular subclasses and network medicine

References

CHAPTER 33: Interplay between hepatitis B virus and innate immune signaling pathways