Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.9
5.1
Journals
Cells
Special Issues
Role of Hyaluronan in Human Health and Disease
share announcement

Role of Hyaluronan in Human Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 7043

Special Issue Editors

Dr. Barbara Triggs-Raine

E-Mail Website
Guest Editor
Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Interests: disorders of hyaluronan metabolism; lysosomal storage disorders
Dr. Soma Meran

E-Mail Website
Guest Editor
School of Medicine, Cardiff University, Cardiff, UK
Interests: hyaluronan; anti-fibrotic; renal disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hyaluronan (HA) is a large carbohydrate polymer that is ubiquitously distributed in mammalian tissues. Its abundance, distribution and size are controlled by proteins and/or mechanical forces that regulate these parameters to allow for normal development and the maintenance of healthy tissues. HA synthesis-related proteins, hyaluronidases and HA-binding proteins are among the critical molecules known to be associated with alterations in HA that drive abnormal development and/or disease.

This Special issue will examine diseases and developmental abnormalities that are the consequences of the disruption of HA homeostasis and the mechanisms that underly these processes. Examples of these diseases include genetic disorders involving components of HA metabolism, cancers, fibrosis-related diseases, disorders of immune function and failures in normal tissue repair/regeneration.

Dr. Barbara Triggs-Raine
Dr. Soma Meran
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hyaluronan
  • hyaluronidases
  • hyaluronan-binding proteins
  • hyaluronan receptors
  • fibrosis
  • cancer
  • development
  • immune function

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

23 pages, 2753 KiB  
Article
A Novel, Cell-Compatible Hyaluronidase Activity Assay Identifies Dextran Sulfates and Other Sulfated Polymeric Hydrocarbons as Potent Inhibitors for CEMIP
by Anja Schmaus, Sofia Spataro, Paul Sallmann, Stephanie Möller, Leonardo Scapozza, Marco Prunotto and Jonathan P. Sleeman
Cells 2025, 14(2), 101; https://doi.org/10.3390/cells14020101 - 11 Jan 2025
Viewed by 542
Abstract
Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology. The hyaluronidase CEMIP requires the presence of living cells for its HA depolymerizing activity. [...] Read more.
Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology. The hyaluronidase CEMIP requires the presence of living cells for its HA depolymerizing activity. CEMIP is overexpressed in a variety of pathological conditions, and the inhibition of its hyaluronidase activity therefore has therapeutic potential. To identify novel inhibitors of the CEMIP hyaluronidase activity, we established here a cell-compatible, medium-throughput assay for CEMIP-dependent HA depolymerization. The assay employs ultrafiltration plates to separate low- from high-molecular-weight HA, followed by quantification of HA fragments using an HA ELISA-like assay. Using this assay, we tested a range of compounds that have been reported to inhibit other hyaluronidases. Thereby, we identified several sulfated hydrocarbon polymers that inhibit CEMIP more potently than other hyaluronidases. One of these is heparin, a sulfated glycosaminoglycan produced by mast cells that constitutes the first described physiological CEMIP inhibitor. The most potent inhibitor (IC50 of 1.8 nM) is dextran sulfate, a synthetic sulfated polysaccharide. Heparin and dextran sulfate are used in numerous established and experimental biomedical applications. Their ability to inhibit CEMIP needs to be taken into account in these contexts. Full article
(This article belongs to the Special Issue Role of Hyaluronan in Human Health and Disease)
►▼ Show Figures

Figure 1

14 pages, 1645 KiB  
Article
Hymecromone Promotes Longevity and Insulin Sensitivity in Mice
by Nadine Nagy, Kathryn S. Czepiel, Gernot Kaber, Darko Stefanovski, Aviv Hargil, Nina Pennetzdorfer, Robert Targ, Saranya C. Reghupaty, Thomas N. Wight, Robert B. Vernon, Rebecca L. Hull-Meichle, Payton Marshall, Carlos O. Medina, Hunter Martinez, Anissa Kalinowski, Rudolph D. Paladini, Stavros Garantziotis, Joshua W. Knowles and Paul L. Bollyky
Cells 2024, 13(20), 1727; https://doi.org/10.3390/cells13201727 - 18 Oct 2024
Viewed by 1611
Abstract
Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find [...] Read more.
Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks (p < 0.0001 by Log-rank Mantel Cox test). The maximum lifespan of 4-MU treated mice increased from 159 to 194 weeks. In tandem with these effects, 4-MU enhances insulin sensitivity, a metabolic parameter known to regulate lifespan, as measured by insulin tolerance testing (ITT) as well as frequent sampling intra venous glucose tolerance tests (FSIVGTTs). We further observed that 4-MU treated mice weigh less while consuming the same amount of food, indicating that 4-MU treatment alters energy expenditure. However, we do not observe changes in tissue HA content in this model. We conclude that 4-MU promotes insulin sensitivity and longevity but that the underlying mechanism, and the contribution of HA is unclear. 4-MU, already approved in various countries for hepatobiliary conditions, is currently under investigation and clinical development as a therapy for several chronic inflammatory conditions. These data suggest that the beneficial effects of 4-MU on tissue metabolism may include effects on longevity. Full article
(This article belongs to the Special Issue Role of Hyaluronan in Human Health and Disease)
►▼ Show Figures

Figure 1

14 pages, 10108 KiB  
Article
Hyaluronan Mediates Cold-Induced Adipose Tissue Beiging
by Xi Chen, Yifan Wang, Huiqiao Li, Yanru Deng, Charlise Giang, Anying Song, Yu’e Liu, Qiong A. Wang and Yi Zhu
Cells 2024, 13(15), 1233; https://doi.org/10.3390/cells13151233 - 23 Jul 2024
Viewed by 1536
Abstract
Adipose tissue beiging refers to the process by which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines, such as classical brown adipocytes, to improve systemic metabolism, which is beneficial for people with obesity and [...] Read more.
Adipose tissue beiging refers to the process by which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines, such as classical brown adipocytes, to improve systemic metabolism, which is beneficial for people with obesity and metabolic diseases. Cold exposure and β3-adrenergic receptor (AR) agonist treatment are two commonly used stimuli for increasing beige adipocytes in mice; however, their underlying biological processes are different. Transcriptional analysis of inguinal white adipose tissue (iWAT) has revealed that changes in extracellular matrix (ECM) pathway genes are specific to cold exposure. Hyaluronic acid (HA), a non-sulfated linear polysaccharide produced by nearly all cells, is one of the most common components of ECM. We found that cold exposure significantly increased iWAT HA levels, whereas the β3-AR agonist CL316,243 did not. Increasing HA levels in iWAT by Has2 overexpression significantly increases cold-induced adipose tissue beiging; in contrast, decreasing HA by Spam1 overexpression, which encodes a hyaluronidase that digests HA, significantly decreases cold-induced iWAT beiging. All these data implicate a role of HA in promoting adipose tissue beiging, which is unique to cold exposure. Given the failure of β3-AR agonists in clinical trials for obesity and metabolic diseases, increasing HA could serve as a new approach for recruiting more beige adipocytes to combat metabolic diseases. Full article
(This article belongs to the Special Issue Role of Hyaluronan in Human Health and Disease)
►▼ Show Figures

Figure 1

Review

Jump to: Research

18 pages, 815 KiB  
Review
Impacts of Hyaluronan on Extracellular Vesicle Production and Signaling
by Melanie A. Simpson
Cells 2025, 14(2), 139; https://doi.org/10.3390/cells14020139 - 18 Jan 2025
Viewed by 533
Abstract
Hyaluronan (HA) is a critical component of cell and tissue matrices and an important signaling molecule. The enzymes that synthesize and process HA, as well as the HA receptors through which the signaling properties of HA are transmitted, have been identified in extracellular [...] Read more.
Hyaluronan (HA) is a critical component of cell and tissue matrices and an important signaling molecule. The enzymes that synthesize and process HA, as well as the HA receptors through which the signaling properties of HA are transmitted, have been identified in extracellular vesicles and implicated in context-specific processes associated with health and disease. The goal of this review is to present a comprehensive summary of the research on HA and its related receptors and enzymes in extracellular vesicle biogenesis and the cellular responses to vesicles bearing these extracellular matrix modulators. When present in extracellular vesicles, HA is assumed to be on the outside of the vesicle and is sometimes found associated with CD44 or the HAS enzyme itself. Hyaluronidases may be inside the vesicles or present on the vesicle surface via a transmembrane domain or GPI linkage. The implication of presenting these signals in extracellular vesicles is that there is a greater range of systemic distribution and more complex delivery media than previously thought for secreted HA or hyaluronidase alone. Understanding the context for these HA signals offers new diagnostic and therapeutic insight. Full article
(This article belongs to the Special Issue Role of Hyaluronan in Human Health and Disease)
►▼ Show Figures

Figure 1

17 pages, 1442 KiB  
Review
Hyaluronic Acid-Based Drug Delivery Systems for Cancer Therapy
by Ekaterina Pashkina, Maria Bykova, Maria Berishvili, Yaroslav Lazarev and Vladimir Kozlov
Cells 2025, 14(2), 61; https://doi.org/10.3390/cells14020061 - 7 Jan 2025
Viewed by 753
Abstract
In recent years, hyaluronic acid (HA) has attracted increasing attention as a promising biomaterial for the development of drug delivery systems. Due to its unique properties, such as high biocompatibility, low toxicity, and modifiability, HA is becoming a basis for the creation of [...] Read more.
In recent years, hyaluronic acid (HA) has attracted increasing attention as a promising biomaterial for the development of drug delivery systems. Due to its unique properties, such as high biocompatibility, low toxicity, and modifiability, HA is becoming a basis for the creation of targeted drug delivery systems, especially in the field of oncology. Receptors for HA overexpressed in subpopulations of cancer cells, and one of them, CD44, is recognized as a molecular marker for cancer stem cells. This review examines the role of HA and its receptors in health and tumors and analyzes existing HA-based delivery systems and their use in various types of cancer. The development of new HA-based drug delivery systems will bring new opportunities and challenges to anti-cancer therapy. Full article
(This article belongs to the Special Issue Role of Hyaluronan in Human Health and Disease)
►▼ Show Figures

Figure 1

17 pages, 2027 KiB  
Review
Genetic Deficiencies of Hyaluronan Degradation
by Stephen P. Fink and Barbara Triggs-Raine
Cells 2024, 13(14), 1203; https://doi.org/10.3390/cells13141203 - 16 Jul 2024
Cited by 2 | Viewed by 1436
Abstract
Hyaluronan (HA) is a large polysaccharide that is broadly distributed and highly abundant in the soft connective tissues and embryos of vertebrates. The constitutive turnover of HA is very high, estimated at 5 g per day in an average (70 kg) adult human, [...] Read more.
Hyaluronan (HA) is a large polysaccharide that is broadly distributed and highly abundant in the soft connective tissues and embryos of vertebrates. The constitutive turnover of HA is very high, estimated at 5 g per day in an average (70 kg) adult human, but HA turnover must also be tightly regulated in some processes. Six genes encoding homologues to bee venom hyaluronidase (HYAL1, HYAL2, HYAL3, HYAL4, HYAL6P/HYALP1, SPAM1/PH20), as well as genes encoding two unrelated G8-domain-containing proteins demonstrated to be involved in HA degradation (CEMIP/KIAA1199, CEMIP2/TMEM2), have been identified in humans. Of these, only deficiencies in HYAL1, HYAL2, HYAL3 and CEMIP have been identified as the cause or putative cause of human genetic disorders. The phenotypes of these disorders have been vital in determining the biological roles of these enzymes but there is much that is still not understood. Deficiencies in these HA-degrading proteins have been created in mice and/or other model organisms where phenotypes could be analyzed and probed to expand our understanding of HA degradation and function. This review will describe what has been found in human and animal models of hyaluronidase deficiency and discuss how this has advanced our understanding of HA’s role in health and disease. Full article
(This article belongs to the Special Issue Role of Hyaluronan in Human Health and Disease)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop