chondroitin-sulfates and Scleroderma--Localized

Despite several investigations, the transcriptional mechanisms which regulate the expression of both type I collagen genes (COL1A1 and COL1A2) in either physiological or pathological situations, such as scleroderma, are not completely known. In this study, we determined the effects of both native ichtyan chondroïtin sulphate (CS) and its derived hydrolytic fragments (CSf) on human normal (NF) and scleroderma (SF) fibroblasts. Here, we demonstrate for the first time that CS and CSf exert an inhibitory effect on type I collagen protein synthesis and decrease the corresponding mRNA steady-state levels of COL1A1 and COL1A2 in NF and SF. These glycosaminoglycan molecules repress COL1A1 gene transcription through a -112/-61 bp sequence upstream the start site of transcription and imply hc-Krox and Sp1 transcription factors. In addition, CS and CSf induced a down-regulation of TbetaRI expression. As a conclusion, our findings highlight a possible new role for CS and CSf as anti-fibrotic molecules and could help in elucidating the mechanisms of action by which CS and CSf exert their inhibitory effect on type I collagen synthesis.

Topics: Base Pairing; Base Sequence; Chondroitin Sulfates; Collagen; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type III; DNA-Binding Proteins; Fibroblasts; Gene Expression Regulation; Humans; Molecular Sequence Data; Peptide Fragments; Promoter Regions, Genetic; Protein Binding; RNA, Messenger; Scleroderma, Localized; Smad Proteins; Sp1 Transcription Factor; Sp3 Transcription Factor; Transcription Factors; Transforming Growth Factor beta

We report a case of atrophoderma of Pasini and Pierini. We determined the glycosaminoglycan content in the involved skin. Dermatan sulfate content in the involved skin (1.88 micrograms uronic acid/mg dry skin) was greater than that in the uninvolved skin (1.05 micrograms uronic acid/mg dry skin). No significant differences in hyaluronic acid, chondroitin sulfate or heparan sulfate content between involved and uninvolved skin were observed. These results suggest that abnormal metabolism of dermatan sulfate may be involved in the pathogenesis of atrophoderma; this pattern has been observed in systemic or localized scleroderma.

Topics: Adult; Atrophy; Chondroitin Sulfates; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Pigmentation Disorders; Scleroderma, Localized; Scleroderma, Systemic; Skin; Uronic Acids

The composition of glycosaminoglycans (GAGs) was analyzed in skin samples of eight patients suffering from localized scleroderma, i.e., three having generalized morphoea and five localized morphoea plaques. From each patients, biopsies were obtained from sclerotic and perilesional areas, and from clinically uninvolved skin of the same region. In the perilesional areas hyaluronic acid concentration was increased (p less than 0.05), while it was decreased (p less than 0.01) in sclerotic areas. Dermatan sulfate concentration was increased in the perilesional (p less than 0.05) as well as in the sclerotic (p less than 0.01) areas. Chondroitin 4/6 sulfate was increased in the sclerotic areas (p less than 0.05). Heparan sulfate showed no changes. No major differences were found in the total concentrations of uronic acid and hexosamine. This study demonstrates that changes in GAG composition in localized scleroderma follow previously described sequences of events of inflammation and fibrosis of connective tissue.

Topics: Adolescent; Adult; Aged; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Hexosamines; Humans; Hyaluronic Acid; Male; Middle Aged; Scleroderma, Localized; Uronic Acids