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Glycosaminoglycans

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (17 December 2021) | Viewed by 36605

Special Issue Editors

Department of Experimental Medicine, University of Campania L. Vanvitelli, Via de Crecchio 7, 80138 Naples, Italy
Interests: glycosaminoglycans; hyaluronic acid; chondroitin; microbial polysaccharide; biosynthetic pathways; GAG-based biomaterials; extracellular matrix; cell-macromolecules interactions
Special Issues, Collections and Topics in MDPI journals
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Via Vivaldi, 43 81100 Caserta, Italy
Interests: metabolic engineering; microbial fermentation; microbial glycosaminoglycans (GAGs) and GAG-like polysaccharides; chondroitin; bioprocess development from lab to pilot scale; probiotics; organic acids; waste biomass valorization
Special Issues, Collections and Topics in MDPI journals
Department of Experimental Medicine, University of Campania L. Vanvitelli, Via de Crecchio 7, 80138 Naples, Italy
Interests: glycosaminoglycans; hyaluronic acid; GAGs in medical devices; GAGs chemical modifications; GAG hydrodynamic characterization; GAG-based hydrogels’ stability, rheology, and interaction with cells; GAG mucoadhesivity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glycosaminoglycans (GAGs) are receiving increasing scientific interest for their structural features, bioactivity, and biochemical role in different physiological and pathological conditions. Structural modifications of well-known GAGs are found in natural sources and/or obtained through custom tailored semisynthetic approaches. The aim of this Special Issue is to cover, with the help and expertise of contributing authors, three main aspects of the ongoing research and innovation on this topic: a) novel biotechnological and biosynthetic strategies to obtain GAG-like molecules; b) innovative approaches in the modification and characterization of GAGs; c) advances in unraveling and exploiting GAGs functional roles in biomedical sciences.

Interest will also be given to innovative aspects related to the biomacromolecules interaction with specific cells targets, towards the assessment of GAGs as effectors in the biochemical cascade.

Prof. Dr. Chiara Schiraldi
Dr. Donatella Cimini
Dr. Annalisa La Gatta
Guest Editors

Manuscript Submission Information

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Keywords

  • biosynthesis of glycosaminoglycans
  • hyaluronan
  • chondroitin sulfate
  • heparin
  • modified GAGS
  • GAGs bioactivity
  • GAGs as biomarkers
  • novel characterization methods
  • GAGs as drug or drug carriers
  • GAGs interaction with cells
  • in vitro cell based assays
  • innovative biofabrication methodology based on GAGs

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Published Papers (12 papers)

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Research

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19 pages, 11459 KiB  
Article
Mutation in the CX3C Motif of G Protein Disrupts Its Interaction with Heparan Sulfate: A Calorimetric, Spectroscopic, and Molecular Docking Study
by Abu Hamza, Abdus Samad, Zahoor Ahmad Parray, Sajda Ara, Anwar Ahmed, Fahad N. Almajhdi, Tajamul Hussain, Asimul Islam and Shama Parveen
Int. J. Mol. Sci. 2022, 23(4), 1950; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23041950 - 09 Feb 2022
Viewed by 2091
Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to [...] Read more.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children and infants. To date, there is no effective vaccine available against RSV. Heparan sulfate is a type of glycosaminoglycan that aids in the attachment of the RSV to the host cell membrane via the G protein. In the present study, the effect of amino acid substitution on the structure and stability of the ectodomain G protein was studied. Further, it was investigated whether mutation (K117A) in the CX3C motif of G protein alters the binding with heparan sulfate. The point mutation significantly affects the conformational stability of the G protein. The mutant protein showed a low binding affinity with heparan sulfate as compared to the wild-type G protein, as determined by fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking studies. The low binding affinity and decreased stability suggested that this mutation may play an important role in prevention of attachment of virion to the host cell receptors. Collectively, this investigation suggests that mutation in the CX3C motif of G protein may likely improve the efficacy and safety of the RSV vaccine. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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21 pages, 9841 KiB  
Article
Potential of Biofermentative Unsulfated Chondroitin and Hyaluronic Acid in Dermal Repair
by Antonella D’Agostino, Annalisa La Gatta, Antonietta Stellavato, Donatella Cimini, Luisana Corsuto, Marcella Cammarota, Maria D’Agostino and Chiara Schiraldi
Int. J. Mol. Sci. 2022, 23(3), 1686; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031686 - 01 Feb 2022
Cited by 5 | Viewed by 2211
Abstract
Chondroitin obtained through biotechnological processes (BC) shares similarities with both chondroitin sulfate (CS), due to the dimeric repetitive unit, and hyaluronic acid (HA), as it is unsulfated. In the framework of this experimental research, formulations containing BC with an average molecular size of [...] Read more.
Chondroitin obtained through biotechnological processes (BC) shares similarities with both chondroitin sulfate (CS), due to the dimeric repetitive unit, and hyaluronic acid (HA), as it is unsulfated. In the framework of this experimental research, formulations containing BC with an average molecular size of about 35 KDa and high molecular weight HA (HHA) were characterized with respect to their rheological behavior, stability to enzymatic hydrolysis and they were evaluated in different skin damage models. The rheological characterization of the HHA/BC formulation revealed a G’ of 92 ± 3 Pa and a G″ of 116 ± 5 Pa and supported an easy injectability even at a concentration of 40 mg/mL. HA/BC preserved the HHA fraction better than HHA alone. BTH was active on BC alone only at high concentration. Assays on scratched keratinocytes (HaCaT) monolayers showed that all the glycosaminoglycan formulations accelerated cell migration, with HA/BC fastening healing 2-fold compared to the control. In addition, in 2D HaCaT cultures, as well as in a 3D skin tissue model HHA/BC efficiently modulated mRNA and protein levels of different types of collagens and elastin remarking a functional tissue physiology. Finally, immortalized human fibroblasts were challenged with TNF-α to obtain an in vitro model of inflammation. Upon HHA/BC addition, secreted IL-6 level was lower and efficient ECM biosynthesis was re-established. Finally, co-cultures of HaCaT and melanocytes were established, showing the ability of HHA/BC to modulate melanin release, suggesting a possible effect of this specific formulation on the reduction of stretch marks. Overall, besides demonstrating the safety of BC, the present study highlights the potential beneficial effect of HHA/BC formulation in different damage dermal models. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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19 pages, 4168 KiB  
Article
Affinity and Specificity for Binding to Glycosaminoglycans Can Be Tuned by Adapting Peptide Length and Sequence
by Helena Crijns, Lowie Adyns, Eva Ganseman, Seppe Cambier, Eline Vandekerckhove, Noëmie Pörtner, Lotte Vanbrabant, Sofie Struyf, Tanja Gerlza, Andreas Kungl and Paul Proost
Int. J. Mol. Sci. 2022, 23(1), 447; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010447 - 31 Dec 2021
Cited by 7 | Viewed by 2001
Abstract
Although glycosaminoglycan (GAG)–protein interactions are important in many physiological and pathological processes, the structural requirements for binding are poorly defined. Starting with GAG-binding peptide CXCL9(74-103), peptides were designed to elucidate the contribution to the GAG-binding affinity of different: (1) GAG-binding motifs (i.e., BBXB [...] Read more.
Although glycosaminoglycan (GAG)–protein interactions are important in many physiological and pathological processes, the structural requirements for binding are poorly defined. Starting with GAG-binding peptide CXCL9(74-103), peptides were designed to elucidate the contribution to the GAG-binding affinity of different: (1) GAG-binding motifs (i.e., BBXB and BBBXXB); (2) amino acids in GAG-binding motifs and linker sequences; and (3) numbers of GAG-binding motifs. The affinity of eight chemically synthesized peptides for various GAGs was determined by isothermal fluorescence titration (IFT). Moreover, the binding of peptides to cellular GAGs on Chinese hamster ovary (CHO) cells was assessed using flow cytometry with and without soluble GAGs. The repetition of GAG-binding motifs in the peptides contributed to a higher affinity for heparan sulfate (HS) in the IFT measurements. Furthermore, the presence of Gln residues in both GAG-binding motifs and linker sequences increased the affinity of trimer peptides for low-molecular-weight heparin (LMWH), partially desulfated (ds)LMWH and HS, but not for hyaluronic acid. In addition, the peptides bound to cellular GAGs with differential affinity, and the addition of soluble HS or heparin reduced the binding of CXCL9(74-103) to cellular GAGs. These results indicate that the affinity and specificity of peptides for GAGs can be tuned by adapting their amino acid sequence and their number of GAG-binding motifs. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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17 pages, 69358 KiB  
Article
Albumin–Hyaluronan Interactions: Influence of Ionic Composition Probed by Molecular Dynamics
by Piotr Bełdowski, Maciej Przybyłek, Przemysław Raczyński, Andra Dedinaite, Krzysztof Górny, Florian Wieland, Zbigniew Dendzik, Alina Sionkowska and Per M. Claesson
Int. J. Mol. Sci. 2021, 22(22), 12360; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212360 - 16 Nov 2021
Cited by 11 | Viewed by 2475
Abstract
The lubrication mechanism in synovial fluid and joints is not yet fully understood. Nevertheless, intermolecular interactions between various neutral and ionic species including large macromolecular systems and simple inorganic ions are the key to understanding the excellent lubrication performance. An important tool for [...] Read more.
The lubrication mechanism in synovial fluid and joints is not yet fully understood. Nevertheless, intermolecular interactions between various neutral and ionic species including large macromolecular systems and simple inorganic ions are the key to understanding the excellent lubrication performance. An important tool for characterizing the intermolecular forces and their structural consequences is molecular dynamics. Albumin is one of the major components in synovial fluid. Its electrostatic properties, including the ability to form molecular complexes, are closely related to pH, solvation, and the presence of ions. In the context of synovial fluid, it is relevant to describe the possible interactions between albumin and hyaluronate, taking into account solution composition effects. In this study, the influence of Na+, Mg2+, and Ca2+ ions on human serum albumin–hyaluronan interactions were examined using molecular dynamics tools. It was established that the presence of divalent cations, and especially Ca2+, contributes mostly to the increase of the affinity between hyaluronan and albumin, which is associated with charge compensation in negatively charged hyaluronan and albumin. Furthermore, the most probable binding sites were structurally and energetically characterized. The indicated moieties exhibit a locally positive charge which enables hyaluronate binding (direct and water mediated). Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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20 pages, 3867 KiB  
Article
The Influences of Sulphation, Salt Type, and Salt Concentration on the Structural Heterogeneity of Glycosaminoglycans
by Suman Samantray, Olujide O. Olubiyi and Birgit Strodel
Int. J. Mol. Sci. 2021, 22(21), 11529; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111529 - 26 Oct 2021
Cited by 12 | Viewed by 1869
Abstract
The increasing recognition of the biochemical importance of glycosaminoglycans (GAGs) has in recent times made them the center of attention of recent research investigations. It became evident that subtle conformational factors play an important role in determining the relationship between the chemical composition [...] Read more.
The increasing recognition of the biochemical importance of glycosaminoglycans (GAGs) has in recent times made them the center of attention of recent research investigations. It became evident that subtle conformational factors play an important role in determining the relationship between the chemical composition of GAGs and their activity. Therefore, a thorough understanding of their structural flexibility is needed, which is addressed in this work by means of all-atom molecular dynamics (MD) simulations. Four major GAGs with different substitution patterns, namely hyaluronic acid as unsulphated GAG, heparan-6-sulphate, chondroitin-4-sulphate, and chondroitin-6-sulphate, were investigated to elucidate the influence of sulphation on the dynamical features of GAGs. Moreover, the effects of increasing NaCl and KCl concentrations were studied as well. Different structural parameters were determined from the MD simulations, in combination with a presentation of the free energy landscape of the GAG conformations, which allowed us to unravel the conformational fingerprints unique to each GAG. The largest effects on the GAG structures were found for sulphation at position 6, as well as binding of the metal ions in the absence of chloride ions to the carboxylate and sulphate groups, which both increase the GAG conformational flexibility. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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17 pages, 2428 KiB  
Article
Phenotypic Characterization of Immortalized Chondrocytes from a Desbuquois Dysplasia Type 1 Mouse Model: A Tool for Studying Defects in Glycosaminoglycan Biosynthesis
by Chiara Gramegna Tota, Beatrice Valenti, Antonella Forlino, Antonio Rossi and Chiara Paganini
Int. J. Mol. Sci. 2021, 22(17), 9304; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179304 - 27 Aug 2021
Cited by 1 | Viewed by 1762
Abstract
The complexity of skeletal pathologies makes use of in vivo models essential to elucidate the pathogenesis of the diseases; nevertheless, chondrocyte and osteoblast cell lines provide relevant information on the underlying disease mechanisms. Due to the limitations of primary chondrocytes, immortalized cells represent [...] Read more.
The complexity of skeletal pathologies makes use of in vivo models essential to elucidate the pathogenesis of the diseases; nevertheless, chondrocyte and osteoblast cell lines provide relevant information on the underlying disease mechanisms. Due to the limitations of primary chondrocytes, immortalized cells represent a unique tool to overcome this problem since they grow very easily for several passages. However, in the immortalization procedure the cells might lose the original phenotype; thus, these cell lines should be deeply characterized before their use. We immortalized primary chondrocytes from a Cant1 knock-out mouse, an animal model of Desbuquois dysplasia type 1, with a plasmid expressing the SV40 large and small T antigen. This cell line, based on morphological and biochemical parameters, showed preservation of the chondrocyte phenotype. In addition reduced proteoglycan synthesis and oversulfation of glycosaminoglycan chains were demonstrated, as already observed in primary chondrocytes from the Cant1 knock-out mouse. In conclusion, immortalized Cant1 knock-out chondrocytes maintained the disease phenotype observed in primary cells validating the in vitro model and providing an additional tool to further study the proteoglycan biosynthesis defect. The same approach might be extended to other cartilage disorders. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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11 pages, 2353 KiB  
Article
Selective Inhibition of Heparan Sulphate and Not Chondroitin Sulphate Biosynthesis by a Small, Soluble Competitive Inhibitor
by Marissa L. Maciej-Hulme, Eamon Dubaissi, Chun Shao, Joseph Zaia, Enrique Amaya, Sabine L. Flitsch and Catherine L. R. Merry
Int. J. Mol. Sci. 2021, 22(13), 6988; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136988 - 29 Jun 2021
Cited by 2 | Viewed by 2397
Abstract
The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds provide cheap alternatives to genetic manipulation methods. However, existing chemical [...] Read more.
The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds provide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole organisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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18 pages, 2848 KiB  
Article
Hyaluronan Hydrogels for Injection in Superficial Dermal Layers: An In Vitro Characterization to Compare Performance and Unravel the Scientific Basis of Their Indication
by Annalisa La Gatta, Maria Aschettino, Antonietta Stellavato, Antonella D’Agostino, Valentina Vassallo, Emiliano Bedini, Gilberto Bellia and Chiara Schiraldi
Int. J. Mol. Sci. 2021, 22(11), 6005; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116005 - 02 Jun 2021
Cited by 7 | Viewed by 3117
Abstract
Background: Skinboosters represent the latest category of hyaluronan (HA) hydrogels released for aesthetic purposes. Different from originally developed gels, they are intended for more superficial injections, claiming a skin rejuvenation effect through hydration and possibly prompting biochemical effects in place of the conventional [...] Read more.
Background: Skinboosters represent the latest category of hyaluronan (HA) hydrogels released for aesthetic purposes. Different from originally developed gels, they are intended for more superficial injections, claiming a skin rejuvenation effect through hydration and possibly prompting biochemical effects in place of the conventional volumetric action. Here, three commercial skinboosters were characterized to unravel the scientific basis for such indication and to compare their performances. Methods: Gels were evaluated for water-soluble/insoluble-HA composition, rheology, hydration, cohesivity, stability and effect, in vitro, on human dermal fibroblasts towards the production of extracellular matrix components. Results: Marked differences in the insoluble-hydrogel amount and in the hydrodynamic parameters for water-soluble-HA chains were evidenced among the gels. Hydration, rigidity and cohesivity also varied over a wide range. Sensitivity to hyaluronidases and Reactive Oxygen Species was demonstrated allowing a stability ranking. Slight differences were found in gels’ ability to prompt elastin expression and in ColIV/ColI ratio. Conclusions. A wide panel of biophysical and biochemical parameters for skinboosters was provided, supporting clinicians in the conscious tuning of their use. Data revealed great variability in gels’ behavior notwithstanding the same clinical indication and unexpected similarities to the volumetric formulations. Data may be useful to improve customization of gel design toward specific uses. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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25 pages, 5771 KiB  
Article
Extracellular Matrix Deposition and Remodeling after Corneal Alkali Burn in Mice
by Kazadi N. Mutoji, Mingxia Sun, Garrett Elliott, Isabel Y. Moreno, Clare Hughes, Tarsis F. Gesteira and Vivien J. Coulson-Thomas
Int. J. Mol. Sci. 2021, 22(11), 5708; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115708 - 27 May 2021
Cited by 17 | Viewed by 2617
Abstract
Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are essential for correct collagen fibrillogenesis and maintaining corneal homeostasis. We investigated the spatial and temporal distribution of [...] Read more.
Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are essential for correct collagen fibrillogenesis and maintaining corneal homeostasis. We investigated the spatial and temporal distribution of glycosaminoglycans (GAGs) and PGs after a chemical injury. The chemical composition of chondroitin sulfate (CS)/dermatan sulfate (DS) and heparan sulfate (HS) were characterized in mouse corneas 5 and 14 days after alkali burn (AB), and compared to uninjured corneas. The expression profile and corneal distribution of CS/DSPGs and keratan sulfate (KS) PGs were also analyzed. We found a significant overall increase in CS after AB, with an increase in sulfated forms of CS and a decrease in lesser sulfated forms of CS. Expression of the CSPGs biglycan and versican was increased after AB, while decorin expression was decreased. We also found an increase in KS expression 14 days after AB, with an increase in lumican and mimecan expression, and a decrease in keratocan expression. No significant changes in HS composition were noted after AB. Taken together, our study reveals significant changes in the composition of the extracellular matrix following a corneal chemical injury. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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Review

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23 pages, 819 KiB  
Review
Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation
by Ryuichi Mashima, Torayuki Okuyama and Mari Ohira
Int. J. Mol. Sci. 2022, 23(4), 1963; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23041963 - 10 Feb 2022
Cited by 7 | Viewed by 2880
Abstract
Heparan sulfate (HS) is a type of glycosaminoglycan that plays a key role in a variety of biological functions in neurology, skeletal development, immunology, and tumor metastasis. Biosynthesis of HS is initiated by a link of xylose to Ser residue of HS proteoglycans, [...] Read more.
Heparan sulfate (HS) is a type of glycosaminoglycan that plays a key role in a variety of biological functions in neurology, skeletal development, immunology, and tumor metastasis. Biosynthesis of HS is initiated by a link of xylose to Ser residue of HS proteoglycans, followed by the formation of a linker tetrasaccharide. Then, an extension reaction of HS disaccharide occurs through polymerization of many repetitive units consisting of iduronic acid and N-acetylglucosamine. Subsequently, several modification reactions take place to complete the maturation of HS. The sulfation positions of N-, 2-O-, 6-O-, and 3-O- are all mediated by specific enzymes that may have multiple isozymes. C5-epimerization is facilitated by the epimerase enzyme that converts glucuronic acid to iduronic acid. Once these enzymatic reactions have been completed, the desulfation reaction further modifies HS. Apart from HS biosynthesis, the degradation of HS is largely mediated by the lysosome, an intracellular organelle with acidic pH. Mucopolysaccharidosis is a genetic disorder characterized by an accumulation of glycosaminoglycans in the body associated with neuronal, skeletal, and visceral disorders. Genetically modified animal models have significantly contributed to the understanding of the in vivo role of these enzymes. Their role and potential link to diseases are also discussed. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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25 pages, 1626 KiB  
Review
Hyaluronan as a Prominent Biomolecule with Numerous Applications in Medicine
by Katarína Valachová and Ladislav Šoltés
Int. J. Mol. Sci. 2021, 22(13), 7077; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137077 - 30 Jun 2021
Cited by 31 | Viewed by 4814
Abstract
Hyaluronan (HA) is a natural glycosaminoglycan present in many tissues of all vertebrates. HA has various biological functions, which are dependent on its molar mass. High-molar-mass HA has anti-angiogenic, immunosuppressive and anti-inflammatory properties, while low-molar-mass HA has opposite effects. HA has also antioxidative [...] Read more.
Hyaluronan (HA) is a natural glycosaminoglycan present in many tissues of all vertebrates. HA has various biological functions, which are dependent on its molar mass. High-molar-mass HA has anti-angiogenic, immunosuppressive and anti-inflammatory properties, while low-molar-mass HA has opposite effects. HA has also antioxidative properties, however on the other hand it can be readily degraded by reactive oxygen species. For many years it has been used in treatment of osteoarthritis, cosmetics and in ophthalmology. In the last years there has been a growing interest of HA to also be applied in other fields of medicine such as skin wound healing, tissue engineering, dentistry and gene delivery. In this review we summarize information on modes of HA administration, properties and effects of HA in various fields of medicine including recent progress in the investigation of HA. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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24 pages, 1102 KiB  
Review
Heparan Sulfate Proteoglycans in Viral Infection and Treatment: A Special Focus on SARS-CoV-2
by Valeria De Pasquale, Miriam Shasa Quiccione, Simona Tafuri, Luigi Avallone and Luigi Michele Pavone
Int. J. Mol. Sci. 2021, 22(12), 6574; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126574 - 18 Jun 2021
Cited by 40 | Viewed by 6388
Abstract
Heparan sulfate proteoglycans (HSPGs) encompass a group of glycoproteins composed of unbranched negatively charged heparan sulfate (HS) chains covalently attached to a core protein. The complex HSPG biosynthetic machinery generates an extraordinary structural variety of HS chains that enable them to bind a [...] Read more.
Heparan sulfate proteoglycans (HSPGs) encompass a group of glycoproteins composed of unbranched negatively charged heparan sulfate (HS) chains covalently attached to a core protein. The complex HSPG biosynthetic machinery generates an extraordinary structural variety of HS chains that enable them to bind a plethora of ligands, including growth factors, morphogens, cytokines, chemokines, enzymes, matrix proteins, and bacterial and viral pathogens. These interactions translate into key regulatory activity of HSPGs on a wide range of cellular processes such as receptor activation and signaling, cytoskeleton assembly, extracellular matrix remodeling, endocytosis, cell-cell crosstalk, and others. Due to their ubiquitous expression within tissues and their large functional repertoire, HSPGs are involved in many physiopathological processes; thus, they have emerged as valuable targets for the therapy of many human diseases. Among their functions, HSPGs assist many viruses in invading host cells at various steps of their life cycle. Viruses utilize HSPGs for the attachment to the host cell, internalization, intracellular trafficking, egress, and spread. Recently, HSPG involvement in the pathogenesis of SARS-CoV-2 infection has been established. Here, we summarize the current knowledge on the molecular mechanisms underlying HSPG/SARS-CoV-2 interaction and downstream effects, and we provide an overview of the HSPG-based therapeutic strategies that could be used to combat such a fearsome virus. Full article
(This article belongs to the Special Issue Glycosaminoglycans)
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