ENHANCED EXPRESSION OF MESSENGER-RNA FOR INSULIN-LIKE GROWTH-FACTOR-I IN POSTBURN HYPERTROPHIC SCAR TISSUE AND ITS FIBROGENIC ROLE BY DERMAL FIBROBLASTS

Hypertrophic scarring (HSc) which frequently develops in patients following severe thermal injury is characterized by accumulation of extracellular matrix (ECM) proteins including type I and type III collagen. In this study, we examined the presence and quantity of IGF-1 mRNA transcripts in post-burn HSc. The results of dot blot experiments showed a 77.5% (100 +/- 8.15 vs 177.5 +/- 19, p<0.01) increase in expression of IGF-1 IIIRNA in HSe tissue relative to normal dermis obtained from the same patients. A Northern blot analysis confirmed the specificity of the IGF-1 cDNA. This cDNA visualized four different transcripts with apparent sizes of 7.0, 3.9, 1.8 and 1.0 kb, similar to those previously reported. The possible fibrogenic role of IGF-1 was examined by analyzing the effect of this growth factor on the expression of mRNA for the pro alpha 1(I) chain of type I procollagen and the pro alpha 1(III) chain of type III procollagen in dermal fibroblasts. IGF-1 increased the expression of these transcripts as early as 6 h and the effect was maximal at 24 h. Quantitative analysis by densitometry showed a 149 and 166% increase in pro alpha 1(I) and pro alpha 1(III) mRNA after 24 h of IGF-1 treatment, respectively. This effect seems to be specific as the abundance of mRNA for the pro alpha 2(I) chain of type I procollagen or TIMP-II was unchanged. When another 4 strains of dermal fibroblasts were treated with IGF-1, a significant increase (16.94 +/- 1.13 vs 10.87 +/- 1.79, p<0.01, N=4) in the expression of type I procollagen mRNA was found. This was consistent with a significant increase in collagen production, as measured by hydroxyproline in conditioned medium (2.04 +/- 0.3 ng/1000 cells vs 1.35 +/- 0.4 ng/1000 cells, p<0.01, N=4). The effects of IGF-1 were temporary, since removal of IGF-1 from media caused a reduction in expression of type I procollagen mRNA to its basal level within 48 h. Enhanced expression of IGF-1 mRNA in post-burn HSc tissues and the potentially fibrogenic effects of this growth factor on dermal fibroblasts, suggest that it could contribute to the accumulation of type I and type III. collagen found in many fibroproliferative disorders such as HSc.