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Expression and localization of insulin-like growth factor-1 in normal and post-burn hypertrophic scar tissue in human

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Abstract

The migration of epithelial cells from dermal appendages toward the wound surface is essential for re-epithelialization of partial thickness burn injuries. This study provides evidence that these cells in vivo synthesize a mitogenic and fibrogenic factor, insulin-like growth factor-1 (IGF-1), which may promote the development of the post-burn fibroproliferative disorder, hypertrophic scarring (HSc). An evaluation of 7 post-burn hypertrophic scars, 7 normal skin samples obtained from the same patients and 4 mature scars revealed that IGF-1 expressing cells from the disrupted sweat glands tend to reform small sweat glands of 4-10 cells/gland in post-burn HSc. The number of these cells increases with time and the glands become larger in mature scar. Other epithelial cells such as those found in sebaceous glands and basal and suprabasal keratinocytes, also express IGF-1 protein and mRNA as detected by Northern and RT-PCR analysis of RNA obtained from whole skin and separated epidermis and dermis. However, cultured keratinocytes did not express mRNA for IGF-1. Histological comparisons between normal and HSc sections show no mature sebaceous glands in dermal fibrotic tissues but the number of IGF-1 producing cells including infiltrated immune cells was markedly higher in the dermis of hypertrophic scar tissues relative to that of the normal control. In these tissues, but not in normal dermis, IGF-1 protein was found associated with the extracellular matrix. By in situ hybridization, IGF-1 mRNA was localized to both epithelial and infiltrated immune cells. Collectively, these findings suggest that in normal skin, fibroblasts have little or no access to diffusible IGF-1 expressed by epithelial cells of the epidermis, sweat and sebaceous glands; while following dermal injury when these structures are disrupted, IGF-1 may contribute to the development of fibrosis through its fibrogenic and mitogenic functions. Reformation of sweat glands during the later stages of healing may, therefore, limit this accessibility, and lead to scar maturation.

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Authors and Affiliations

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

    Aziz Ghahary, You J. Shen, Rijian Wang & Edward E. Tredget

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

    Edward E. Tredget

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

    Paul G. Scott

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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., Wang, R. et al. Expression and localization of insulin-like growth factor-1 in normal and post-burn hypertrophic scar tissue in human. Mol Cell Biochem 183, 1–9 (1998). https://doi.org/10.1023/A:1006890212478

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