COLLAGENASE PRODUCTION IS LOWER IN POSTBURN HYPERTROPHIC SCAR FIBROBLASTS THAN IN NORMAL FIBROBLASTS AND IS REDUCED BY INSULIN-LIKE GROWTH-FACTOR-I

We recently demonstrated that the accumulation of extracellular matrix in post-burn hypertrophic scarring (HSc) tissues is, in part, caused by an overexpression of mRNA for fibronectin, type I, and type III pro collagen. Here, we report that five different fibroblast cell strains derived from HSc tissues are deficient in collagenase activity relativ e to paired fibroblasts from normal skin of the same patients, Quantit ative analysis demonstrated significantly lower (52.5 +/- 16.8% vs 100 +/- 8.3%; n = 9; p < 0.05) collagenase activity in conditioned medium from HSc fibroblasts relative to that obtained from the control. The expression of collagenase mRNA was also significantly depressed (51 +/ - 7% vs 100 +/- 11%; n 5; p < 0.05) in four of five strains of HSc fib roblasts examined. The level of mRNA for collagenase in both HSc and n ormal fibroblasts increased with serial passage, but at any given pass age number, the expression of this transcript was lower in HSc fibrobl asts. Insulin-like growth factor 1 (IGF-1), which is present at the si te of HSc in high quantity, reduced collagenase mRNA but increased typ e I collagen mRNA expression in a time-dependent manner, The collagena se activity in conditioned medium derived from IGF-1-treated normal de rmal fibroblasts was reduced (23.1 +/- 7.81% m 100 +/- 6.6%; n = 7; p < 0.05), A significant reduction in collagenase mRNA and activity was also found in HSc fibroblasts following IGF-1 treatment, These finding s suggest that IGF-1-induced suppression of collagenase mRNA and activ ity may be a mechanism by which IGF-1 promotes the development of post -burn HSc.