Disease relevance of SDC3

• All malignant glioma cell lines and glioblastoma specimens expressed all types of syndecan mRNA, except in one glioma cell line that lacked syndecan-3 expression [1].
• Objective: The objective of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) in SDC3 are associated with obesity in the Korean population [2].
• Approximately 20% of chondrocytes were immunopositive for syndecan-3 in normal human articular cartilage, the number of syndecan-3-expressing chondrocytes significantly increased during the progression of osteoarthritis with more than 80% syndecan-3-positive cells in the upper zone of severely affected osteoarthritic cartilage [3].

High impact information on SDC3

• Cultured HSC showed a membranous staining pattern for syndecan-1, syndecan-3, and heparan sulfate, and in addition intracellular staining for syndecan-2, -3, and 4 [4].
• In acinar zone 1, large stimulated macrophages and HSC, present in increased numbers, were strongly positive for syndecan-3 [4].
• CONCLUSION: Our results show the selective induction of a CXCL8 binding site on endothelial syndecan-3 in RA synovium [5].
• Induction of a CXCL8 binding site on endothelial syndecan-3 in rheumatoid synovium [5].
• Using antibodies to syndecan-1-4 and glypican-1, -3, and -4, the selective expression of syndecan-3 by endothelial cells was detected in RA and nonrheumatoid synovia [5].

Biological context of SDC3

• Additionally, transient transfection experiments suggest a role of human syndecan-3 in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism [6].
• The similarity of the cloned DNA sequence with that of other mammalian species and the high expression in the nervous system led us to the assumption that human syndecan-3 could perform comparable functions to those described for syndecan-3 in rat and mouse [6].
• Next, all three nonsynonymous SNPs [T271I (rs2282440, C>T), D245N (rs4949184, C>T), and V150I (rs2491132, C>T)] in the SDC3 gene in control female subjects (BMI < 23, n = 229) and obese female subjects (BMI > 30, n = 245) were genotyped [2].
• We found that the topographical location of proliferating chondrocytes in developing chick long bones changes with increasing embryonic age and that syndecan-3 gene expression changes in a comparable manner [7].
• These results indicate that syndecan-3 interferes with the interaction of BMP2 with its receptors, and that this interference results in an inhibition of chondrogenesis [8].

Anatomical context of SDC3

• In addition, RT-PCR showed the presence of syndecan-3 messenger RNA in endothelial cells extracted from RA and nonrheumatoid synovia [5].
• When different cell lines were transiently transfected with full-length syndecan-3 cDNA, it was localized to the membrane and induced the formation of long filopodia-like structures, microspikes, and varicosities [6].
• Consequently, the actin cytoskeleton was re-organized, since actin staining was mostly found in the cellular extensions and at the cell periphery, co-localizing with the syndecan-3 staining [6].
• Syndecan-3 mRNA is mostly expressed in the nervous system, the adrenal gland, and the spleen [6].
• Syndecan-3 is a selective regulator of chondrocyte proliferation [7].

Associations of SDC3 with chemical compounds

• We expressed domains of the core protein of the transmembrane heparan sulfate proteoglycan N-syndecan (syndecan-3) either individually or as maltose-binding protein fusion proteins [9].
• Immature proliferating chondrocyte populations reared in growth-promoting culture conditions displayed strong continuous syndecan-3 gene expression; upon induction of maturation by vitamin C treatment, syndecan-3 gene expression was markedly down-regulated [10].
• In this report, we explore the possibility of whether the four tyrosine residues in the cytoplasmic domain of N-syndecan (Syndecan 3) are potential substrates for phosphorylation by a tyrosine kinase [11].
• Microbeads coated with MK or poly-L-lysine induced clustering of glypican-2 as well as syndecan-3 [12].
• Together, these results suggest that Schwann cells bind to collagen type V via syndecan-3-dependent binding to a novel high affinity heparin binding site in the alpha4(V)-NTD [13].

Physical interactions of SDC3

• MK bound to heparan sulfate chains of glypican-2 in a manner similar to syndecan-3 [12].

Regulatory relationships of SDC3

• Treatment with FGF-2 for 24 h stimulated both syndecan-3 gene expression and chondrocyte proliferation; this growth stimulation was counteracted by cotreatment with heparinase I or III [10].

Other interactions of SDC3

• Syndecan-3 and perlecan expression in tumours was found in an expected distribution pattern [14].
• Double-staining techniques showed that heparan sulfate was found predominantly at the basal aspect of the endothelium and suggested that syndecan-3 might function as one of the proteoglycans involved in FGF-2 signaling in the endothelium [15].
• The syndecan-3 antibodies interfered only with FGF-2 mitogenic action, but not that of insulin-like growth factor-1 or parathyroid hormone [7].
• In addition, we observed different localization of epitope-tagged glypican-2 and syndecan-3 on the surface of N2a cells; the result suggested that they may play different roles in MK-mediated neural function [12].
• These syndecan-3-rich proliferating chondrocytes lay beneath developing articular chondrocytes rich in their typical matrix protein tenascin-C, resulting in a striking boundary between these two populations of chondrocytes [10].

Analytical, diagnostic and therapeutic context of SDC3

• Affinity chromatography of Schwann cell detergent extracts on a column of immobilized alpha4(V)-NTD resulted in the isolation of syndecan-3, a transmembrane heparan sulfate proteoglycan [13].
• Double immunofluorescence for heparanase and syndecan-3 revealed colocalization of the proteins in cell bodies of neurons and oligodendrocytes, suggestive of constitutive expression in these cell types [16].
• At labour, a co-localization of syndecan 3 and connexin 43 could be demonstrated in the smooth muscle by confocal microscopy [17].

References