Comparison of the effects of dexamethasone and 13-cis-retinoic acid on connective tissue biosynthesis in human skin fibroblasts

Abstract

The effects of glucocorticoids and retinoids on connective tissue biosynthesis were studied in cultured human skin fibroblasts (HSFs). More specifically attention was paid to the effects of dexamethasone and 13-cis-retinoic acid (RA) on total protein and collagen synthesis and on collagen and fibronectin mRNA levels. The results indicated that dexamethasone reduced the relative collagen synthesis and collagen mRNA levels in HSFs and increased the total incorporation of proline into proteins, the latter effect being due to increased activity in the intracellular proline pool. 13-cis-RA did not affect collagen synthesis at the concentration studied (10(-7) M) but it did reduce the corresponding mRNA levels. Simultaneous addition of both dexamethasone and 13-cis-RA or etretinate resulted in the largest decrease in type I and type III procollagen mRNA levels, indicating that retinoids do not oppose the effect of glucocorticoids on collagen synthesis in cultured HSFs. For comparison the effects of dexamethasone and 13-cis-RA on the mRNA levels of another extracellular matrix component, fibronectin, and of a constitutive enzyme, glyceraldehyde-3-phosphate dehydrogenase, were also studied. The results indicated, that dexamethasone treatment did not alter fibronectin mRNA levels in HSFs, while 13-cis-RA did so to a marked extent. Both dexamethasone and 13-cis-RA also reduced the mRNA level of glyceraldehyde-3-phosphate dehydrogenase, indicating that glucocorticoids and retinoids have both similar and different effects on gene expression in HSF.