EXPRESSION AND LOCALIZATION OF INSULIN-LIKE GROWTH-FACTOR-I IN NORMALAND POSTBURN HYPERTROPHIC SCAR TISSUE IN HUMAN

The migration of epithelial cells from dermal appendages toward the wo und 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, insulinlike growth facto r-1 (IGF-1), which may promote the development of the post-burn fibrop roliferative 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 epitheli al cells such as those found in sebaceous glands and basal and supraba sal keratinocytes, also express IGF-1 protein and mRNA as detected by Northern and RT-PCR analysis of RNA obtained from whole skin and separ ated epidermis and dermis. However, cultured keratinocytes did not exp ress mRNA for IGF-1. Histological comparisons between normal and HSc s ections show no mature sebaceous glands in dermal fibrotic tissues but the number of IGF-1 producing cells including infiltrated immune cell s was markedly higher in the dermis of hypertrophic scar tissues relat ive to that of the normal control. In these tissues, but not in normal dermis, IGF-1 protein was found associated with the extracellular mat rix. By in situ hybridization, IGF-1 mRNA was localized to both epithe lial and infiltrated immune cells. Collectively, these findings sugges t that in normal skin, fibroblasts have little or no access to diffusi ble IGF-1 expressed by epithelial cells of the epidermis, sweat and se baceous glands; while following dermal injury when these structures ar e disrupted, IGF-1 may contribute to the development of fibrosis throu gh its fibrogenic and mitogenic functions. Reformation of sweat glands during the later stages of healing may, therefore, limit this accessi bility, and lead to scar maturation.