A biological guide to glycosaminoglycans: current perspectives and pending questions

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(15), P. 3331 - 3366

Published: March 18, 2024

Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that covalently attached to core proteins form proteoglycans (PGs). This article summarizes key biological findings for the most widespread GAGs, namely HA, chondroitin sulfate/dermatan sulfate (CS/DS), keratan (KS), and heparan (HS). It focuses on major processes remain be deciphered get a comprehensive view of mechanisms mediating GAG functions. They include regulation biosynthesis postsynthetic modifications in heparin (HP) HS, composition, heterogeneity, function tetrasaccharide linkage region its role disease, functional characterization new PGs recently identified by glycoproteomics, selectivity interactions mediated chains, display chains at cell surface their impact availability activity soluble ligands, move through glycocalyx layer reach receptors, human profile health roles GAGs particular (syndecans, decorin, biglycan) involved cancer, inflammation, fibrosis, possible use as disease biomarkers, design inhibitors targeting biosynthetic enzymes GAG-protein develop novel therapeutic approaches.

Language: Английский

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The Role of Fibroblasts in Skin Homeostasis and Repair

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1586 - 1586

Published: July 17, 2024

Fibroblasts are typical mesenchymal cells widely distributed throughout the human body where they (1) synthesise and maintain extracellular matrix, ensuring structural role of soft connective tissues; (2) secrete cytokines growth factors; (3) communicate with each other cell types, acting as signalling source for stem niches; (4) involved in tissue remodelling, wound healing, fibrosis, cancer. This review focuses on developmental heterogeneity dermal fibroblasts, their ability to sense changes biomechanical properties surrounding aging, skin repair, pathologic conditions tumour development. Moreover, we describe use fibroblasts different models (e.g., vivo animal vitro systems from 2D 6D cultures) bioengineering informative potential high-throughput assays study under disease contexts personalized healthcare regenerative medicine applications.

Language: Английский

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Decorin suppresses tumor lymphangiogenesis: A mechanism to curtail cancer progression

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(18)

Published: April 23, 2024

The complex interplay between malignant cells and the cellular molecular components of tumor stroma is a key aspect cancer growth development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed stromal cells, affects in its form interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to context-dependent protracted cessation oncogenic RTK activity attenuating their ability drive prosurvival program sustain proangiogenic network. Through unbiased transcriptomic analysis using deep RNAseq, we identified that down-regulated cluster tumor-associated genes involved lymphatic vessel (LV) development when systemically delivered mice harboring breast carcinoma allografts. We found Lyve1 Podoplanin, two established markers LVs, were markedly suppressed at both mRNA protein levels, this suppression correlated significant reduction LVs. further decorin, but not homologous biglycan, inhibited LV sprouting ex vivo 3D model lymphangiogenesis. Mechanistically, interacted vascular endothelial factor 3 (VEGFR3), main RTK, was required for decorin-mediated block Finally, part degraded via decorin-evoked autophagy nutrient- energy-independent manner. findings implicate biological antilymphangiogenic provide potential therapeutic agent curtailing metastasis.

Language: Английский

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Proteoglycans in mechanobiology of tissues and organs: Normal functions and mechanopathology

Proteoglycan Research, Journal Year: 2024, Volume and Issue: 2(2)

Published: April 1, 2024

Proteoglycans (PGs) are a diverse class of glycoconjugates that serve critical functions in normal mechanobiology and mechanopathology. Both the protein cores attached glycosaminoglycan (GAG) chains function mechanically-sensitive processes, loss either can contribute to development pathological conditions. PGs as key components extracellular matrix (ECM) where they mechanosensors mechanosensitive tissues including bone, cartilage, tendon, blood vessels soft organs. The mechanical properties these depend on presence PGs, which play important roles tissue elasticity, osmolarity pressure sensing, response physical activity. Tissue responses cell surface mechanoreceptors include integrins, CD44, voltage sensitive ion channels, transient receptor potential (TRP) piezo channels. molecular interplay wound healing, fibrosis, cancer, transduce ECM influence progression various context-specific conditions diseases. most vary depending its functional needs. Perlecan, for example, is basement membranes, cardiac skeletal muscle, while aggrecan plays primary role cartilage joints. A variety techniques have been used study atomic force microscopy, mouse knockout models,

Language: Английский

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Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy

Proteoglycan Research, Journal Year: 2024, Volume and Issue: 2(3)

Published: June 29, 2024

Anti-angiogenic therapy is an established method for the treatment of several cancers and vascular-related diseases. Most agents employed target vascular endothelial growth factor A, major cytokine stimulating angiogenesis. However, efficacy these treatments limited by onset drug resistance. Therefore, it fundamental importance to better understand mechanisms that regulate angiogenesis microenvironmental cues play significant role influence patient outcome. In this context, here we review three basement membrane heparan sulfate proteoglycans (HSPGs), namely perlecan, agrin collagen XVIII. These HSPGs are abundantly expressed in vasculature and, due their complex molecular architecture, they interact with multiple cell receptors, deeply affecting function. Under normal conditions, exert pro-angiogenic functions. pathological conditions such as cancer inflammation, extracellular matrix remodeling leads degradation large precursor molecules liberation bioactive processed fragments displaying potent angiostatic activity. unexpected functions have been demonstrated C-terminal perlecan XVIII, endorepellin endostatin. can also induce autophagy cells which contributes angiostasis. Overall, affect counterbalancing signals during tumor progression, represent possible means develop new prognostic biomarkers novel therapeutic approaches solid tumors.

Language: Английский

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Pivotal roles of biglycan and decorin in regulating bone mass, water retention, and bone toughness

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 2, 2025

Abstract Proteoglycans, key components of non-collagenous proteins in the bone matrix, attract water through their negatively charged glycosaminoglycan chains. Among these proteoglycans, biglycan (Bgn) and decorin (Dcn) are major subtypes, yet distinct roles remain largely elusive. In this study, we utilized single knockout (KO) mouse models successfully generated double KO (dKO) despite challenges with low yield. Bgn deficiency, but not Dcn decreased trabecular mass, more pronounced loss dKO mice. Low-field nuclear magnetic resonance measurements showed a marked decrease bound among all groups, especially Moreover, both mice exhibited reduced fracture toughness compared to was significantly upregulated mice, while modest upregulation observed indicating Bgn’s predominant role bone. High resolution atomic force microscopy situ permanent energy dissipation increased elastic modulus extrafibrillar matrix / deficient which were diminished upon dehydration. Furthermore, found that indispensable for activation ERK p38 MAPK signaling pathways. Collectively, our results highlight maintaining structure, retention, bulk/in tissue properties exerting influence.

Language: Английский

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Comprehensive Investigation of Proteoglycan Gene Expression in Breast Cancer: Discovery of a Unique Proteoglycan Gene Signature Linked to the Malignant Phenotype

Proteoglycan Research, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 1, 2025

Solid tumors present a formidable challenge in oncology, necessitating innovative approaches to improve therapeutic outcomes. Proteoglycans, multifaceted molecules within the tumor microenvironment, have garnered attention due their diverse roles cancer progression. Their unique ability interact with specific membrane receptors, growth factors, and cytokines provides promising avenue for development of recombinant proteoglycan-based therapies that could enhance precision efficacy treatment. In this study, we performed comprehensive analysis proteoglycan gene landscape human breast carcinomas. Leveraging available wealth genomic clinical data regarding expression carcinoma using machine learning model, identified signature composed five proteoglycans differentially modulated tissue: Syndecan-1 asporin (upregulated) decorin, PRELP podocan (downregulated). Additional query revealed serglycin, previously shown be increased patients mouse models correlate poor prognosis, was indeed decreased vast majority its levels inversely correlated progression invasion. This provide novel diagnostic capabilities biology highlights need further utilization publicly datasets validation preclinical experimental results.

Language: Английский

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Synthesis of three-dimensional matrices based on collagen–pectin–polyacrylate grafted copolymers using the RbTe1.5W0.5O6 photocatalyst

Proceedings of universities Applied chemistry and biotechnology, Journal Year: 2025, Volume and Issue: 14(4), P. 556 - 566

Published: Jan. 13, 2025

The development of new promising materials three-dimensional structure from available bioresorbable, biointegrable and biocompatible polymers is in demand relevant connection with the intensive regenerative medicine. In this work, hydrogels grafted copolymers methyl methacrylate/butyl acrylate onto a mixture collagen pectin were obtained during photocatalysis presence complex oxide RbTe 1.5 W 0.5 O 6 . characteristics synthesis products by gel penetrating chromatography, elemental analysis, electron microscopy, biological biocidality tests. content an amount less than 40%, microstructure polymer form fine-mesh, biocidity sample films established. product was identified on catalyst surface after separation powder aqueous dispersion. main advantage such unique combination properties their components assembled into specific structure. advantages material include, among other things, environmental initial - natural renewable raw materials: isolated cod processing waste, fruit vegetable waste.

Language: Английский

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Contribution of Proteoglycans to the Multiscale Structure and Function of Soft Tissues

Published: Jan. 1, 2025

Language: Английский

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CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity

Journal of Neuroscience Research, Journal Year: 2024, Volume and Issue: 102(7)

Published: July 1, 2024

Abstract Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior tissue function. The CNS/PNS extracellular matrix (ECM) is a dynamic, responsive, highly interactive, space‐filling, cell supportive, stabilizing structure maintaining compartments, ionic microenvironments, microgradients that regulate neuronal activity maintain the neuron in an optimal microenvironment. contains high glycosaminoglycan content (60% hyaluronan, HA) range of PGs. Immobilization HA brain tissues by interactive hyalectan PGs preserves hydration activity, paucity results pro‐convulsant epileptic phenotype. Diverse CS, KS, HSPGs stabilize blood–brain barrier neurovascular unit, provide smart gel neurotransmitter vesicle storage delivery, organize neuromuscular junction basement membrane, motor synaptic plasticity, photoreceptor functions. PG‐HA networks fluxes compartments contribute to membrane polarization dynamics essential activation neurotransduction. Hyalectans form neuroprotective perineuronal nets contributing memory, cognitive learning. Sialoglycoprotein associated with cones rods (SPACRCAN), binding CSPG, stabilizes inter‐photoreceptor ECM. pikachurin eyes shut synapse aiding phototransduction neurotransduction retinal bipolar neurons crucial visual acuity. This achieved through Laminin G motifs pikachurin, shut, neurexins interact dystroglycan–cytoskeleton–ECM‐stabilizing interconnections, specificity, co‐ordination regulatory action potentials neural networks.

Language: Английский

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