Collagenase production is lower in post-burn hypertrophic scar fibroblasts than in normal fibroblasts and is reduced by insulin-like growth factor-1.
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 procollagen. Here, we report that five different fibroblast cell strains derived from HSc tissues are deficient in collagenase activity relative to paired fibroblasts from normal skin of the same patients. Quantitative 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 fibroblasts examined. The level of mRNA for collagenase in both HSc and normal fibroblasts increased with serial passage, but at any given passage number, the expression of this transcript was lower in HSc fibroblasts. Insulin-like growth factor 1 (IGF-1), which is present at the site of HSc in high quantity, reduced collagenase mRNA but increased type I collagen mRNA expression in a time-dependent manner. The collagenase activity in conditioned medium derived from IGF-1-treated normal dermal fibroblasts was reduced (23.1 +/- 7.81% vs 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 findings suggest that IGF-1-induced suppression of collagenase mRNA and activity may be a mechanism by which IGF-1 promotes the development of post-burn HSc.
Ghahary
A
A
Department of Surgery, University of Alberta, Edmonton, Canada.
Shen
Y J
YJ
Nedelec
B
B
Wang
R
R
Scott
P G
PG
Tredget
E E
EE
D000293:Adolescent; D000328:Adult; D002056:Burns / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D017439:Cicatrix, Hypertrophic / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D003094:Collagen / Q000235:genetics; D017364:Collagenases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D017364:Collagenases