Expression of Glycosaminoglycan-Related Genes and the Role of Polyamines in the Glycosaminoglycan Biosynthetic Pathways

Abstract

Glycosaminoglycans (GAGs), a group of structurally related acidic polysaccharides, are primarily present as glycan moieties of proteoglycans (PGs). The physiological functions of PGs depend on the interaction between the glycan moieties and proteins such as growth factors, chemokines, and adhesion molecules. For this reason, the sulfation pattern, the degree of epimerization, and the glycan moiety chain length impact their interactions with GAG-binding proteins. Although the structural changes in GAGs occur during the development and aging process, their detailed mechanisms are not fully understood. This review provides an overview of the heparan sulfate (HS)-and chondroitin sulfate (CS)-related gene expression at the transcriptional and translational level. In addition, it also describes the molecular mechanisms of the polyamine stimulation of glycosaminoglycan synthesis. HS biosynthesis was initiated once N-acetylglucosamine (GlcNAc) is transferred by EXTL3 to the common linkage tetrasaccharides, glucuronic acid (GlcA)β1-3galactose (Gal)β1-3Galβ1-4-xylose (Xyl)β1-O-Ser in PGs (19). Chain elongation is catalyzed by the EXT1/EXT2 heterodimer through the alternate addition of GlcNAc and GlcA residues (19). If GlcNAc is transferred to the linkage region by EXTL2, initiation of chain elongation is inhibited. HS backbone is epimerized and sulfated by

Qualitative and quantitative analyses in sulfated glycosaminoglycans, chondroitin sulfate/dermatan sulfate, during 3T3‐L1 adipocytes differentiation

“…Compositions of the unsaturated disaccharides in CS vary among the cell lines, but the ΔO unit (ΔDi-0S), ΔA unit (ΔDi-4S), or ΔC unit (ΔDi-6S) are the major three disaccharides (Higashi, 2020). By using the adipogenic-induction medium to promote cell differentiation, our results also showed a significant change in its composition between both groups.…”

“…The composition of the unsaturated disaccharides of CS/DS in 3T3‐L1 preadipocytes was revealed in our study, demonstrating the ∆A unit [GlcA‐GalNAc(4S) and IdoA‐GalNAc(4S)] (calculated from A + iA units) as the major CS/DS disaccharides in 3T3‐L1 cell line that reached 89% and 86% in ND and DI groups, respectively (Figure 4c). Compositions of the unsaturated disaccharides in CS vary among the cell lines, but the ∆O unit (∆Di‐0S), ∆A unit (∆Di‐4S), or ∆C unit (∆Di‐6S) are the major three disaccharides (Higashi, 2020). By using the adipogenic‐induction medium to promote cell differentiation, our results also showed a significant change in its composition between both groups.…”