ALTERED DERMATAN SULFATE PROTEOGLYCAN SYNTHESIS IN FIBROBLAST-CULTURES ESTABLISHED FROM SKIN OF PATIENTS WITH SYSTEMIC-SCLEROSIS

Objective. To study whether changes in the properties of skin from pat ients with systemic sclerosis (SSc) are the result of altered metaboli sm of dermatan sulfate proteoglycans. Methods. Fibroblast cultures wer e established from skin of healthy controls, and from affected and una ffected skin of patients with SSc. Synthesized proteoglycans were labe led with H-3 glucosamine and S-35 sulfate. The amount of mRNA of the d ifferent dermatan sulfate proteoglycans was determined by hybridizatio n with the corresponding cDNA probes. Results. A 2-fold increase in se cretion of total proteoglycans was found in cell cultures from affecte d and normal appearing skin from patients with SSc. The production of 2 different dermatan sulfate proteoglycans was increased. Aggrecan/ver sican increased 4-fold and decorin 2-fold in cultures of affected skin from patients with SSc. The mRNA for decorin increased 3-fold, while the mRNA level for versican increased only slightly. Similar but less marked changes were noted in cultures from normal appearing skin. in c ontrast, the biglycan mRNA level decreased and the product could only be found in very small amounts in SSc cultures. Conclusion. This marke d alteration of dermatan sulfate proteoglycan metabolism distinguishes nest only affected skin but also normal appearing SSc skin from that of controls. The altered proteoglycan production may affect organizati on of matrix fibers and thereby the fibrotic process observed in patie nts with SSc.