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Biomolecules
Special Issues
Hyaluronic Acid and Proteoglycans: Basic and Biomedical Applications
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Hyaluronic Acid and Proteoglycans: Basic and Biomedical Applications

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Carbohydrates".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 9722

Special Issue Editor

Dr. Michele Scuruchi

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Interests: inflammation; cell signalling pathways; vascular proteoglycans and glycosaminoglycans in the initiation and progression of vascular damage; structure, function, immunological and biological properties of hyaluronic acid and proteoglycans in arthritis

Special Issue Information

Dear Colleagues,

Hyaluronic acid (HA) is a member of the glycosaminoglycans (GAGs), constitutive of the extracellular matrix (ECM). HA is a linear non-sulphated polysaccharide that provides compression strength, lubrication, and hydration within the ECM. Besides its structural role, HA is also an active signalling molecule that plays an important role in some biological activities including cell adhesion and motility, proliferation, and differentiation. HA functions are closely related to its molecular weight. For example, high-molecular-weight HA hampers cell proliferation and migration, showing anti-inflammatory and immunosuppressive properties, whereas low-molecular-weight HA enhances cell proliferation and could be considered a pro-inflammatory molecule.

Proteoglycans (PGs) are complex macromolecules composed by a central protein core decorated with covalently linked GAGs chains. According to a recent classification, PGs may be grouped in four major classes with distinct forms and functions: the intracellular, cell-surface, pericellular, and extracellular proteoglycans. Because of their ability to interact with a wide array of molecules, they are involved in a plethora of biological functions including development, inflammation, cancer, and angiogenesis.

This Special Issue invites submissions of original papers and reviews that cover any innovative research on the role of HA and PGs in matrix remodelling, homeostasis and signalling, studies addressing HA and PGs as potential therapeutic targets, biomarkers, and their use in regenerative medicine and other related subjects.

Dr. Michele Scuruchi
Guest Editor

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. Biomolecules is an international peer-reviewed open access monthly 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

  • hyaluronic acid
  • proteoglycans
  • GAGs
  • extracellular matrix
  • hyaluronic acid and proteoglycans in disease
  • cancer
  • inflammation
  • angiogenesis
  • vascular homeostasis and damage
  • arthritis and arthrosis
  • glycobiology

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Published Papers (4 papers)

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Research

16 pages, 3551 KiB  
Article
Cant1 Affects Cartilage Proteoglycan Properties: Aggrecan and Decorin Characterization in a Mouse Model of Desbuquois Dysplasia Type 1
by Chiara Gramegna Tota, Alessandra Leone, Asifa Khan, Antonella Forlino, Antonio Rossi and Chiara Paganini
Biomolecules 2024, 14(9), 1064; https://doi.org/10.3390/biom14091064 - 26 Aug 2024
Viewed by 3587
Abstract
Desbuquois dysplasia type 1 (DBQD1) is a recessive chondrodysplasia caused by mutations in the CANT1 gene, encoding for the Golgi Calcium-Activated Nucleotidase 1 (CANT1). The enzyme hydrolyzes UDP, the by-product of glycosyltransferase reactions, but it might play other roles in different cell types. [...] Read more.
Desbuquois dysplasia type 1 (DBQD1) is a recessive chondrodysplasia caused by mutations in the CANT1 gene, encoding for the Golgi Calcium-Activated Nucleotidase 1 (CANT1). The enzyme hydrolyzes UDP, the by-product of glycosyltransferase reactions, but it might play other roles in different cell types. Using a Cant1 knock-out mouse, we demonstrated that CANT1 is crucial for glycosaminoglycan (GAG) synthesis; however, its impact on the biochemical properties of cartilage proteoglycans remains unknown. Thus, in this work, we characterized decorin and aggrecan from primary chondrocyte cultures and cartilage biopsies of mutant mice at post-natal day 4 by Western blots and further investigated their distribution in the cartilage extracellular matrix (ECM) by immunohistochemistry. We demonstrated that the GAG synthesis defect caused by CANT1 impairment led to the synthesis and secretion of proteoglycans with shorter GAG chains compared with wild-type animals. However, this alteration did not result in the synthesis and secretion of decorin and aggrecan in the unglycanated form. Interestingly, the defect was not cartilage-specific since also skin decorin showed a reduced hydrodynamic size. Finally, immunohistochemical studies in epiphyseal sections of mutant mice demonstrated that the proteoglycan structural defect moderately affected decorin distribution in the ECM. Full article
(This article belongs to the Special Issue Hyaluronic Acid and Proteoglycans: Basic and Biomedical Applications)
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20 pages, 4792 KiB  
Article
The Expression of Serglycin Is Required for Active Transforming Growth Factor β Receptor I Tumorigenic Signaling in Glioblastoma Cells and Paracrine Activation of Stromal Fibroblasts via CXCR-2
by Dimitra Manou, Maria-Angeliki Golfinopoulou, Sara Naif D. Alharbi, Hind A. Alghamdi, Fatimah Mohammed Alzahrani and Achilleas D. Theocharis
Biomolecules 2024, 14(4), 461; https://doi.org/10.3390/biom14040461 - 10 Apr 2024
Cited by 1 | Viewed by 1667
Abstract
Serglycin (SRGN) is a pro-tumorigenic proteoglycan expressed and secreted by various aggressive tumors including glioblastoma (GBM). In our study, we investigated the interplay and biological outcomes of SRGN with TGFβRI, CXCR-2 and inflammatory mediators in GBM cells and fibroblasts. SRGN overexpression is associated [...] Read more.
Serglycin (SRGN) is a pro-tumorigenic proteoglycan expressed and secreted by various aggressive tumors including glioblastoma (GBM). In our study, we investigated the interplay and biological outcomes of SRGN with TGFβRI, CXCR-2 and inflammatory mediators in GBM cells and fibroblasts. SRGN overexpression is associated with poor survival in GBM patients. High SRGN levels also exhibit a positive correlation with increased levels of various inflammatory mediators including members of TGFβ signaling pathway, cytokines and receptors including CXCR-2 and proteolytic enzymes in GBM patients. SRGN-suppressed GBM cells show decreased expressions of TGFβRI associated with lower responsiveness to the manipulation of TGFβ/TGFβRI pathway and the regulation of pro-tumorigenic properties. Active TGFβRI signaling in control GBM cells promotes their proliferation, invasion, proteolytic and inflammatory potential. Fibroblasts cultured with culture media derived by control SRGN-expressing GBM cells exhibit increased proliferation, migration and overexpression of cytokines and proteolytic enzymes including CXCL-1, IL-8, IL-6, IL-1β, CCL-20, CCL-2, and MMP-9. Culture media derived by SRGN-suppressed GBM cells fail to induce the above properties to fibroblasts. Importantly, the activation of fibroblasts by GBM cells not only relies on the expression of SRGN in GBM cells but also on active CXCR-2 signaling both in GBM cells and fibroblasts. Full article
(This article belongs to the Special Issue Hyaluronic Acid and Proteoglycans: Basic and Biomedical Applications)
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14 pages, 959 KiB  
Article
Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis
by Elżbieta Lato-Kariakin, Kornelia Kuźnik-Trocha, Anna Gruenpeter, Katarzyna Komosińska-Vassev, Krystyna Olczyk and Katarzyna Winsz-Szczotka
Biomolecules 2023, 13(12), 1737; https://doi.org/10.3390/biom13121737 - 2 Dec 2023
Viewed by 1387
Abstract
(1) Background: In this study, we evaluated the modulation of urine glycosaminoglycans (GAGs), which resulted from etanercept (ETA) therapy in patients with juvenile idiopathic arthritis (JIA) in whom methotrexate therapy failed to improve their clinical condition. (2) Methods: The sulfated GAGs (sGAGs, by [...] Read more.
(1) Background: In this study, we evaluated the modulation of urine glycosaminoglycans (GAGs), which resulted from etanercept (ETA) therapy in patients with juvenile idiopathic arthritis (JIA) in whom methotrexate therapy failed to improve their clinical condition. (2) Methods: The sulfated GAGs (sGAGs, by complexation with blue 1,9-dimethylmethylene), including chondroitin–dermatan sulfate (CS/DS) and heparan sulfate (HS), as well as non-sulfated hyaluronic acid (HA, using the immunoenzymatic method), were determined in the blood of 89 children, i.e., 30 healthy children and 59 patients with JIA both before and during two years of ETA treatment. (3) Results: We confirmed the remodeling of the urinary glycan profile of JIA patients. The decrease in the excretion of sGAGs (p < 0.05), resulting from a decrease in the concentration of the dominant fraction in the urine, i.e., CS/DS (p < 0.05), not compensated by an increase in the concentration of HS (p < 0.000005) and HA (p < 0.0005) in the urine of patients with the active disease, was found. The applied biological therapy, leading to clinical improvement in patients, at the same time, did not contribute to normalization of the concentration of sGAGs (p < 0.01) in the urine of patients, as well as CS/DS (p < 0.05) in the urine of sick girls, while it promoted equalization of HS and HA concentrations. These results indicate an inhibition of the destruction of connective tissue structures but do not indicate their complete regeneration. (4) Conclusions: The metabolisms of glycans during JIA, reflected in their urine profile, depend on the patient’s sex and the severity of the inflammatory process. The remodeling pattern of urinary glycans observed in patients with JIA indicates the different roles of individual types of GAGs in the pathogenesis of osteoarticular disorders in sick children. Furthermore, the lack of normalization of urinary GAG levels in treated patients suggests the need for continued therapy and continuous monitoring of its effectiveness, which will contribute to the complete regeneration of the ECM components of the connective tissue and thus protect the patient against possible disability. Full article
(This article belongs to the Special Issue Hyaluronic Acid and Proteoglycans: Basic and Biomedical Applications)
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13 pages, 3081 KiB  
Article
Endocan Knockdown Down-Regulates the Expression of Angiogenesis-Associated Genes in Il-1ß Activated Chondrocytes
by Michele Scuruchi, Federica Aliquò, Angela Avenoso, Giuseppe Mandraffino, Giovanna Vermiglio, Aurelio Minuti, Salvatore Campo, Giuseppe Maurizio Campo and Angela D’Ascola
Biomolecules 2023, 13(5), 851; https://doi.org/10.3390/biom13050851 - 18 May 2023
Cited by 2 | Viewed by 1916
Abstract
Endocan is a small soluble proteoglycan (PG) known to be involved in inflammation and angiogenesis. Increased endocan expression was found in the synovia of arthritic patients and chondrocytes stimulated with IL-1ß. Considering these findings, we aimed to investigate the effects of endocan knockdown [...] Read more.
Endocan is a small soluble proteoglycan (PG) known to be involved in inflammation and angiogenesis. Increased endocan expression was found in the synovia of arthritic patients and chondrocytes stimulated with IL-1ß. Considering these findings, we aimed to investigate the effects of endocan knockdown on the modulation of pro-angiogenic molecules expression in a model of IL-1ß-induced inflammation in human articular chondrocytes. Endocan, VEGF-A, MMP-9, MMP-13, and VEGFR-2 expression was measured in both normal and endocan knockdown chondrocytes stimulated with IL-1ß. VEGFR-2 and NF-kB activation were also measured. Results have shown that endocan, VEGF-A, VEGFR-2, MMP-9, and MMP-13 were significantly up-regulated during IL-1ß-induced inflammation; interestingly, the expression of such pro-angiogenic molecules and NF-kB activation were significantly reduced by endocan knockdown. These data support the hypothesis that endocan released by activated chondrocytes may be involved in the mechanisms that stimulate cell migration and invasion, as well as angiogenesis, in the pannus of arthritic joints. Full article
(This article belongs to the Special Issue Hyaluronic Acid and Proteoglycans: Basic and Biomedical Applications)
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