DIFFERENTIAL REGULATION OF DECORIN AND BIGLYCAN GENE-EXPRESSION BY DEXAMETHASONE AND RETINOIC ACID IN CULTURED HUMAN SKIN FIBROBLASTS

Proteoglycans participate in the assembly of extracellular matrix, dir ectly by interacting with other matrix components and indirectly by re gulating cellular growth-factor responses. We have studied the regulat ion of gene expression of two small extracellular matrix chondroitin/d ermatan sulfate proteoglycans, decorin and biglycan, by dexamethasone and retinoic acid in cultured human skin fibroblasts. Dexamethasone in creased decorin production, maximally 4.8-fold, and decorin mRNA level s up to 2.3-fold, but had no effect on biglycan production or mRNA lev els. Dexamethasone also prevented transforming growth factor-beta-elic ited down-regulation of decorin mRNA levels and production by dermal f ibroblasts. In addition, dexamethasone potently inhibited enhancement of biglycan production and mRNA levels by transforming growth factor-b eta. Retinoic acid dose dependently reduced decorin mRNA levels (by 51 %) and production (by 72%), but had no effect on biglycan gene express ion. Retinoic acid did not alter the effect of transforming growth fac tor-beta on decorin or biglycan production or mRNA levels. These resul ts provide evidence that the effects of glucocorticoids and retinoids on dermal connective tissue are partially mediated via altered express ion of decorin and biglycan, which both in turn regulate the activity of transforming growth factor-beta, the most potent stimulator of conn ective tissue deposition.