Showing papers on "Keratan sulfate published in 2021"

Glycosaminoglycan-Protein Interactions: The First Draft of the Glycosaminoglycan Interactome.

Abstract: The six mammalian glycosaminoglycans (GAGs), chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate, are linear polysaccharides. Except for hyaluronan, they are sulfated to various extent, and covalently attached to proteins to form proteoglycans. GAGs interact with growth factors, morphogens, chemokines, extracellular matrix proteins and their bioactive fragments, receptors, lipoproteins, and pathogens. These interactions mediate their functions, from embryonic development to extracellular matrix assembly and regulation of cell signaling in various physiological and pathological contexts such as angiogenesis, cancer, neurodegenerative diseases, and infections. We give an overview of GAG-protein interactions (i.e., specificity and chemical features of GAG- and protein-binding sequences), and review the available GAG-protein interaction networks. We also provide the first comprehensive draft of the GAG interactome composed of 832 biomolecules (827 proteins and five GAGs) and 932 protein-GAG interactions. This network is a scaffold, which in the future should integrate structures of GAG-protein complexes, quantitative data of the abundance of GAGs in tissues to build tissue-specific interactomes, and GAG interactions with metal ions such as calcium, which plays a major role in the assembly of the extracellular matrix and its interactions with cells. This contextualized interactome will be useful to identify druggable GAG-protein interactions for therapeutic purpose.

Glycosaminoglycans: Sweet as Sugar Targets for Topical Skin Anti-Aging

Abstract: Glycosaminoglycans (GAGs) are long, linear polysaccharides comprised of repeating disaccharide units with pleiotropic biological functions, with the non-sulfated GAG hyaluronic acid (HA), and sulfated GAGs dermatan sulfate, chondroitin sulfate, heparan sulfate, keratan sulfate, and to a lesser extent heparin all being expressed in skin. Their ability to regulate keratinocyte proliferation and differentiation, inflammatory processes and extracellular matrix composition and quality demonstrates their critical role in regulating skin physiology. Similarly, the water-binding properties of GAGs and structural qualities, particularly for HA, are crucial for maintaining proper skin form and hydration. The biological importance of GAGs, as well as extensive evidence that their properties and functions are altered in both chronological and extrinsic skin aging, makes them highly promising targets to improve cosmetic skin quality. Within the present review, we examine the cutaneous biological activity of GAGs alongside the protein complexes they form called proteoglycans and summarize the age-related changes of these molecules in skin. We also examine current topical interventional approaches to modulate GAGs for improved skin quality such as direct exogenous administration of GAGs, with a particular interest in strategies targeted at potentiating GAG levels in skin through either attenuating GAG degradation or increasing GAG production.

Novel Insight Into Glycosaminoglycan Biosynthesis Based on Gene Expression Profiles.

Abstract: Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate, except for hyaluronan that is a free polysaccharide, are covalently attached to core proteins to form proteoglycans. More than 50 gene products are involved in the biosynthesis of GAGs. We recently developed a comprehensive glycosylation mapping tool, GlycoMaple, for visualization and estimation of glycan structures based on gene expression profiles. Using this tool, the expression levels of GAG biosynthetic genes were analyzed in various human tissues as well as tumor tissues. In brain and pancreatic tumors, the pathways for biosynthesis of chondroitin and dermatan sulfate were predicted to be upregulated. In breast cancerous tissues, the pathways for biosynthesis of chondroitin and dermatan sulfate were predicted to be up- and down-regulated, respectively, which are consistent with biochemical findings published in the literature. In addition, the expression levels of the chondroitin sulfate-proteoglycan versican and the dermatan sulfate-proteoglycan decorin were up- and down-regulated, respectively. These findings may provide new insight into GAG profiles in various human diseases including cancerous tumors as well as neurodegenerative disease using GlycoMaple analysis.

Extracellular Matrix Deposition and Remodeling after Corneal Alkali Burn in Mice.

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 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.

Keratan sulfate as a marker for medullary bone in fossil vertebrates.

Abstract: The ability to determine the sex of extinct dinosaurs by examining the bones they leave behind would revolutionize our understanding of their paleobiology; however, to date, definitive sex-specific skeletal traits remain elusive or controversial. Although living dinosaurs (i.e., extant birds) exhibit a sex-specific tissue called medullary bone that is unique to females, the confident identification of this tissue in non-avian archosaurs has proven a challenge. Tracing the evolution of medullary bone is complicated by existing variation of medullary bone tissues in living species; hypotheses that medullary bone structure or chemistry varied during its evolution; and a lack of studies aimed at distinguishing medullary bone from other types of endosteal tissues with which it shares microstructural and developmental characteristics, such as pathological tissues. A recent study attempted to capitalize on the molecular signature of medullary bone, which, in living birds, contains specific markers such as the sulfated glycosaminoglycan keratan sulfate, to support the proposed identification of medullary bone of a non-avian dinosaur specimen (Tyrannosaurus rex MOR 1125). Purported medullary bone samples of MOR 1125 reacted positively to histochemical analyses and the single pathological control tested (avian osteopetrosis) did not, suggesting the presence of keratan sulfate might serve to definitively discriminate these tissues for future studies. To further test these results, we sampled 20 avian bone pathologies of various etiologies (18 species), and several MB samples. Our new data universally support keratan sulfate as a reliable marker of medullary bone in birds. However, we also find that reactivity varies among pathological bone tissues, with reactivity in some pathologies indistinguishable from MB. In the current sample, some pathologies comprised of chondroid bone (often a major constituent of skeletal pathologies and developing fracture calluses in vertebrates) contain keratan sulfate. We note that beyond chemistry, chondroid bone shares many characteristics with medullary bone (fibrous matrix, numerous and large cell lacunae, potential endosteal origin, trabecular architecture) and medullary bone has even been considered by some to be a type of chondroid bone. Our results suggest that the presence of keratan sulfate is not exclusive evidence for MB, but rather must be used as one in a suite of criteria available for identifying medullary bone (and thus gravid females) in non-avian dinosaur specimens. Future studies should investigate whether there are definite chemical or microstructural differences between medullary bone and reactive chondroid bone that can discriminate these tissues.

Glycan Epitopes on 201B7 Human-Induced Pluripotent Stem Cells Using R-10G and R-17F Marker Antibodies.

Abstract: We developed two human-induced pluripotent stem cell (hiPSC)/human embryonic stem cell (hESC)-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we investigated the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated from 201B7 cells. The protein yielded a single but very broad band from 480 to 1236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G-positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.