Hyaluronan: Structure, Biology and Biotechnology

Description

This book addresses the structural and biological properties of the extracellular matrix component and glycosaminoglycan polymer hyaluronan (or hyaluronic acid, HA). The book discusses various aspects of HA biology, e.g., HA synthesis and degradation, as well as the role of HA in embryogenesis, development, and cell maintenance. The reader will learn about the role of HA in different tissues as well as its biological activities triggered by the interaction with different HA receptors. A closer look is had at the involvement of HA in human pathologies such as cancer, kidney fibrosis and wound healing. Biotechnological and biomedical applications for HA such as scaffold generation and drug delivery, including the novel synthetic sulphated HA are explored. This work will appeal to a wide readership within the extracellular matrix and hyaluronan field. It can serve as an introduction to the field for junior scientists but can also help senior scientists to gain a broader view of the field beyond their area of specialization. The series Biology of Extracellular Matrix is published in collaboration with the American Society for Matrix Biology and the International Society for Matrix Biology. Preface Contents Chapter 1: Biochemistry of Hyaluronan Synthesis 1.1 Introduction 1.2 Chemistry of the Polymerization 1.3 Enzymes Involved in HA Synthesis 1.3.1 HASes 1.3.2 UGPP and UGDH 1.3.3 The Hexosamine Biosynthetic Pathway 1.3.4 Regulation of the HAS2 Enzyme References Chapter 2: Update on Hyaluronan in Development 2.1 Introduction 2.2 HA: A Versatile Component of ECM 2.3 HA in Fertility 2.4 HA in Organogenesis: The Heart 2.5 HA in Organogenesis: The Gut and Its Vasculature 2.6 HA in Angiogenesis 2.7 HA in Neonatal Development 2.8 Conclusions References Chapter 3: Long Noncoding RNAs and Epigenetic Regulation of Hyaluronan Synthesis 3.1 Introduction 3.2 lncRNAs Classification and Functions 3.3 HAS2-AS1 and Epigenetics 3.4 HAS2-AS1 in Pathologies 3.5 Concluding Remarks References Chapter 4: The Hyaluronan-Rich Zones of Plasma Membrane Protrusions and Extracellular Vesicles 4.1 Hyaluronan-Rich Glycocalyx 4.2 Hyaluronan-Dependent Plasma Membrane Protrusions 4.2.1 Regulation of Filopodia Formation 4.2.2 HA Induces Filopodial Growth and Maintenance 4.2.3 Role of HA as a General Structural Component of the Filopodia 4.2.4 Challenges in the Research Methods of HA-Rich Filopodia 4.2.5 Role of HAS Isoenzymes on the HA Coating, Filopodia, and EVs 4.2.6 HA Receptors and Filopodia 4.3 Discovery of HA-Coated Extracellular Vesicles 4.3.1 Extracellular Vesicles as Novel Messengers 4.3.2 HA Accelerates its Own Accumulation on the EVs 4.4 EV Shedding from the Tips of Plasma Membrane Protrusions 4.5 Hyaluronan Receptors and EVs 4.5.1 HA-Receptors as Cargos of EVs 4.5.2 Is CD44 a Homing Receptor for EVs? 4.6 Physiobiological Properties of HA-EVs 4.7 Clinical Utilization of HA Coating on EV Surfaces 4.7.1 Biomarkers 4.7.2 Utilization of HA-EV as Drug Carriers 4.7.3 Tissue Engineering 4.8 Conclusions References Chapter 5: Hyaluronan in Kidney Fibrosis 5.1 Introduction 5.1.1 HA in Kidney Development 5.2 Chronic Kidney Disease 5.3 Causes of CKD 5.4 Fibrosis: Dysregulated Wound Healing 5.5 Myofibroblasts 5.6 The Mechanisms Controlling TGFβ-Induced Myofibroblast Differentiation 5.7 HA Synthesis: The Hyaluronan Synthase (HAS) Genes 5.8 Transcriptional Regulation 5.9 microRNA Regulation 5.10 HA Cell Surface Assembly 5.11 BMP7 and Fibrosis Prevention and Reversal 5.12 Hyaluronidase-2 (HYAL2) and the Kidney 5.13 Conclusions References Chapter 6: Inter-α-inhibitor Proteins: A Review of Structure and Function 6.1 Introduction 6.2 Molecular Structure of IAIP 6.3 Heavy Chain Isoforms 6.4 Biosynthesis of IAIP 6.5 Regulation of IAIP Biosynthesis 6.6 Metabolism and Excretion of IAIP 6.7 IAIP Function 6.8 Interactions of IAIP and its Components with Extracellular Matrix Components 6.9 Interactions of IAIP and its Components with Coagulation Factors and Complement 6.10 Interactions of IAIP and its Components with Danger-Associated Molecular Patterns and Pathogen-Associated Molecular Patte... 6.11 Effects of IAIP and its Components on Differentiated Cell and Stem Cell Growth 6.12 Associations of IAIP Genetics and Biology with Disease 6.13 Conclusions and Future Directions References Chapter 7: CD44: Does CD44v6 Adversely Impact the Prognosis of Cancer Patients? 7.1 Introduction 7.2 Structure of CD44/CD44 Variants 7.3 Ligands of CD44/CD44 Variants 7.4 CD44/CD44v6-associated Signaling Pathways 7.5 Defining CICs Association with Niche 7.6 CD44/CD44v6 Defines CICs 7.7 CD44/CD44v6 Is a Functional Marker for CICs 7.8 Role of CD44/CD44v6 in Interaction of CICs-Niche with Tumor Microenvironment 7.9 Role of CD44/CD44v6 in Transcriptional Modulation Through Regulation of Transcription Factors 7.10 CD44/CD44v6 as a Biomarker 7.11 CD44/CD44v6 as Therapeutic Target 7.11.1 Inhibition of Hyaluronan /CD44 Interactions 7.11.2 CD44v6 Peptide-Approach 7.11.3 Tissue-Specific Inhibition of CD44 Expression 7.12 Significance References Chapter 8: The Pharmacokinetics and Pharmacodynamics of 4-Methylumbelliferone and its Glucuronide Metabolite in Mice 8.1 Introduction 8.2 Materials and Methods 8.2.1 Mice 8.2.2 4-MU and 4-MUG Treatment 8.2.3 Pharmacokinetic Study in CD-1 Mice for 4-MU 8.2.4 Caco-2 Permeability Assessment 8.2.5 Take Away Study 8.2.6 Built-up Study 8.2.7 Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) Analysis of 4-MU and 4-MUG Concentrations in Mouse Serum 8.2.8 Pharmacokinetic Analysis 8.2.9 Statistical Analysis 8.3 Results 8.3.1 4-MU Administration i.v. and p.o., 4-MU Measured 8.3.2 4-MU Administration i.v. and p.o., 4-MUG Measured 8.3.3 4-MU and 4-MUG Concentration in Mice over Time after 4-MU i.v. and p.o. Administration 8.3.4 4-MUG Administration i.v. and p.o., 4-MUG Measured 8.3.5 4-MUG Administration i.v. and p.o., 4-MU Measured 8.3.6 4-MUG and 4-MU Concentration in Mice over Time after 4-MUG I.V. and P.O. Administration 8.3.7 4-MU and 4-MUG Permeability Assessment 8.3.8 4-MU and 4-MUG Treatment Stop Study 8.3.9 4-MU and 4-MUG Treatment Built-up Study 8.4 Discussion References Chapter 9: The Role of Hyaluronan in Skin Wound Healing 9.1 Introduction 9.1.1 Skin Wound Healing 9.1.2 HA Structure, Synthesis, and Degradation 9.2 HA in the Skin 9.2.1 Location/Distribution in Normal Skin 9.3 HA in Skin Wound Healing 9.3.1 Role of HA in Hemostasis and the Inflammatory Phase of Wound Healing 9.3.2 Role of HA During the Proliferative Phase of Wound Healing 9.3.3 Role of HA in the Remodeling Phase of Wound Healing 9.3.4 HA in Diabetic Wounds 9.4 HA in Topical Wound Dressings 9.5 Conclusion References Chapter 10: Sulfated Hyaluronan: A Novel Player in Cancer Therapeutic and Bioengineering Approaches 10.1 Introduction 10.2 Structural Modification of HA by Incorporation of Sulfate Groups 10.3 The Role of Sulfated HA in Cancer 10.4 Sulfated HA in Matrix-Based Biomaterials 10.5 Concluding Remarks and Perspectives References