EXPRESSION OF COLLAGENASE AND STROMELYSIN IN SKIN FIBROBLASTS FROM RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Collagenase and stromelysin expression in recessive dystrophic epidermolysis bullosa (RDEB) was studied at both the protein and the gene expression levels in fibroblast cultures. The amount of enzyme protein in the culture medium, as determined using a specific enzyme assay, showed a 9.7-fold increase in collagenase and a 2.7-fold increase in stromelysin in RDEB fibroblasts (n = 4 patients) compared with controls (n = 3 subjects with normal skin). Collagenase activity was extremely high in all RDEB fibroblasts. Gene expression, as assessed by Northern blot hybridization, was increased in two sets of RDEB fibroblasts with respect to collagenase, and in two other sets of RDEB fibroblasts with respect 60 stromelysin. The effect of interleukin-1 alpha (IL-1 alpha) on metalloproteinase expression was also examined. The results revealed that: 1) collagenase and stromelysin expression was variably increased at both the protein and the gene expression levels in RDEB fibroblasts; (2) the gene expression level did not always reflect the corresponding protein level; and (3) IL-1 alpha produced a differential effect on collagenase and stromelysin expression. Although the causative gene for RDEB is a type VII collagen, the abnormal expression of collagenase and/or stromelysin is still important in considering the pathophysiology of RDEB.