- Dermatan sulfate is a sulfated glycosaminoglycan (GAG) widely distributed in connective tissues, particularly in the skin, blood vessels, heart valves, tendons, and lungs.
- Structurally, it consists of repeating disaccharide units composed of iduronic acid (IdoA) and N-acetylgalactosamine (GalNAc), with varying degrees of sulfation. What distinguishes dermatan sulfate from other GAGs is the presence of iduronic acid, which is formed from glucuronic acid through epimerization. This structural feature, along with diverse sulfation patterns, gives dermatan sulfate flexibility and conformational adaptability, enabling it to interact with a wide range of proteins, including growth factors, cytokines, adhesion molecules, and coagulation factors.
- In the body, dermatan sulfate is usually attached to core proteins, forming dermatan sulfate proteoglycans such as decorin, biglycan, and versican, which are critical for extracellular matrix (ECM) organization and tissue integrity. These proteoglycans regulate collagen fibrillogenesis, influence cell–matrix interactions, and modulate signaling pathways involved in wound repair and fibrosis. Decorin, for example, binds to transforming growth factor-β (TGF-β), regulating its activity and thus controlling processes like scar formation and tissue remodeling.
- Dermatan sulfate has important roles in coagulation and vascular biology. It enhances the activity of heparin cofactor II, a serine protease inhibitor that specifically inactivates thrombin, thereby contributing to anticoagulant mechanisms and maintaining blood fluidity. This anticoagulant activity distinguishes dermatan sulfate from heparin and heparan sulfate, which primarily act through antithrombin III. Its presence in blood vessel walls highlights its role in vascular homeostasis and protection against thrombosis.
- Clinically, abnormalities in dermatan sulfate metabolism are associated with lysosomal storage disorders, particularly mucopolysaccharidoses (MPS) types I, II, and VI. In these disorders, deficiencies in lysosomal enzymes prevent proper degradation of dermatan sulfate, leading to its accumulation in tissues and organs. This accumulation results in skeletal abnormalities, cardiovascular problems, and progressive organ dysfunction. Measurement of dermatan sulfate levels in urine or blood is therefore used as a diagnostic biomarker for these conditions.
- In wound healing and tissue repair, dermatan sulfate contributes to cell migration, proliferation, and angiogenesis. By interacting with growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF), it helps regulate tissue regeneration and vascularization. Its ability to bind to inflammatory mediators also makes it a key player in modulating immune responses and fibrosis.
- From a therapeutic perspective, dermatan sulfate and its derivatives have been investigated for their anticoagulant, anti-inflammatory, and antifibrotic properties. They show promise in cardiovascular medicine as alternatives to heparin, with potentially lower bleeding risks. In regenerative medicine, dermatan sulfate-containing biomaterials are being explored for scaffolds that mimic the extracellular matrix and support cell growth, particularly in skin and vascular tissue engineering.
