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Enhanced expression of mRNA for insulin-like growth factor-1 in post-burn hypertrophic scar tissue and its fibrogenic role by dermal fibroblasts

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Abstract

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 HSc 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 α1(I) chain of type I procollagen and the pro α1(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 α1(I) and pro α1(III) mRNA after 24 h of IGF-1 treatment, respectively. This effect seems to be specific as the abundance of mRNA for the pro α2(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.

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Authors and Affiliations

  1. Department of Surgery, University of Alberta, T6G 2B7, Edmonton, Alberta, Canada

    Aziz Ghahary, You J. Shen & Bernadette Nedelec

  2. Division of Plastic and Reconstructive Surgery Division of Critical Care, University of Alberta, T6G 2B7, Edmonton, Alberta, Canada

    Paul G. Scott & Edward E. Tredget

  3. Department of Oral Biology, University of Alberta, T6G 2B7, Edmonton, Alberta, Canada

    Aziz Ghahary, You J. Shen, Bernadette Nedelec, Paul G. Scott & Edward E. Tredget

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  1. Aziz Ghahary
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  2. You J. Shen
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  4. Paul G. Scott
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  5. Edward E. Tredget
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Ghahary, A., Shen, Y.J., Nedelec, B. et al. Enhanced expression of mRNA for insulin-like growth factor-1 in post-burn hypertrophic scar tissue and its fibrogenic role by dermal fibroblasts. Mol Cell Biochem 148, 25–32 (1995). https://doi.org/10.1007/BF00929499

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  • DOI: https://doi.org/10.1007/BF00929499

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