DIFFERENTIAL EXPRESSION OF IGFBPS BY NORMAL AND HYPERTROPHIC SCAR FIBROBLASTS

Insulin-like growth factor-I (IGF-I) is a potent fibroblast mitogen wh ich influences wound healing. IGF action is regulated by a family of s ix IGF-binding proteins (IGFBPs). The purpose of this study was to det ermine if expression of IGFBPs is altered in hypertrophic scarring, a wound-healing condition commonly associated with deep dermal injury. F ibroblast populations from the superficial and deep dermal layers of n ormal human skin (SN and DN, respectively) and from superficial and de ep layers of hypertrophic scars (SSc and DSc, respectively) were estab lished and cultured in serum-free medium with or without several growt h factors known to modulate wound healing, including basic fibroblast growth factor, the BB isoform of platelet-derived growth factor, IGF-I , and transforming growth factor-beta (TGF-beta). IGFBP release was an alyzed by radioligand blot assays of culture media. Two main forms of IGFBPs were released, IGFBP-3 and a 24-kDa form which comigrated with serum IGFBP-4. DSc fibroblasts accumulated significantly more IGFBP-3 into serum-free culture medium than did SN, DN, or SSc fibroblasts in all conditions except TGF-beta treatment and confluence. Additionally, comparisons of IGFBP-3 release by each cell type with and without TGF -beta revealed TGF-beta stimulated IGFBP-3 accumulation by SN and DN f ibroblasts but not by SSc or DSc fibroblasts. DN and DSc fibroblasts a ccumulated significantly more of the 24-kDa IGFBP species than SN or S Sc fibroblasts in all conditions except TGF-beta or IGF-I treatment. T hese findings indicate that superficial and deep dermal fibroblasts ar e heterogeneous with respect to IGFBP release, and suggest that hypert rophic scar fibroblasts may represent a population of cells with regul atory properties distinct from those of normal dermal fibroblasts. (C) 1996 Academic Press, Inc.