iduronate and Skin-Diseases

Diabetic foot ulcer (DFU) is a common high-risk complication in patients with diabetes mellitus, but current drugs and therapies in management of this disease cannot meet the urgent clinical needs. In this study, a snail glycosaminoglycan (SGAG) from the cultured China white jade snail was purified and structurally clarified. This snail glycosaminoglycan is a regular sulfated polysaccharide, composed of iduronic acid (IdoA) and N-acetyl-glucosamine (GlcNAc) with the repeating sequence of →4)-α-GlcNAc (1→4)-α-IdoA2S (1→. The biological assays showed that SGAG had no anticoagulant activity for lacking specific heparin pentasaccharide sequence. The pharmacological experiments suggested that SGAG markedly accelerated the healing of full-thickness wounds in diabetic mice skin. Histologic and immunohistochemical analysis revealed that SGAG treatment alleviated the inflammation and dermal edema, and promoted angiogenesis. This is the first report applying the snail glycosaminoglycan to favor diabetic wound healing.

Topics: Acetylglucosamine; Actins; Angiogenesis Inducing Agents; Animals; Anti-Inflammatory Agents; Diabetes Mellitus, Experimental; Edema; Epithelium; Glycosaminoglycans; Heparin; Iduronic Acid; Inflammation; Interleukin-8; Magnetic Resonance Spectroscopy; Male; Mice; Platelet Endothelial Cell Adhesion Molecule-1; Regeneration; Skin; Skin Diseases; Snails; Wound Healing

The properties of [35S]sulfate-labeled proteoglycans secreted by normal human skin fibroblasts were compared with those synthesized by fibroblasts from three patients with Coffin-Lowry syndrome. 60-80% of secreted radioactive macromolecules from normal fibroblasts were eluted from a Sepharose CL-4B column with a mean Kav-value of 0.56 (pool 2); 3-10% of the radioactivity appeared in the exclusion volume of the column (pool 1). In contrast, 17-60% of the proteoglycans from the patients were found in the void volume. The bulk of remaining material was eluted with a mean Kav-value of 0.47. Pool 2 glycan chains from two patients exhibited an increased hydrodynamic size. Pool 1 from normal cells contained predominantly a glucuronic acid-rich proteodermatan sulfate, iduronic acid amounting for approximately 20% of glucuronic acid. In the respective proteodermatan sulfate from the patients, the relative iduronic acid content was at least 33% of that of glucuronic acid. Pool 2 material of all cell lines was characterized predominantly as iduronic acid-rich proteodermatan sulfate. In the proteoglycans from two patients the content of chondroitin 4-sulfate-derived disaccharides was increased at the expense of 6-sulfated chondroitin disaccharides. Native proteoglycans from the patients were less efficiently endocytosed by fibroblasts than their normal counterparts. Coffin-Lowry fibroblasts had a normal capability to synthesize glycosaminoglycan chains on an artificial acceptor, p-nitrophenyl-beta-D-xyloside. They were also normal in 3'-phosphoadenylylsulfate: chondroitin 4- and 6-sulfotransferase activities.

Topics: Abnormalities, Multiple; Adult; Bone and Bones; Cells, Cultured; Child, Preschool; Chondroitin; Dermatan Sulfate; Fibroblasts; Glucuronates; Glucuronic Acid; Humans; Iduronic Acid; Intellectual Disability; Male; Proteoglycans; Sex Factors; Skin; Skin Diseases; Syndrome