Differential expression of IGFBPs by normal and hypertrophic scar fibroblasts

Insulin-like growth factor-I (IGF-I) is a potent fibroblast mitogen which influences wound healing. IGF action is regulated by a family of six IGF-binding proteins (IGFBPs). The purpose of this study was to determine if expression of IGFBPs is altered in hypertrophic scarring, a wound-healing condition commonly associated with deep dermal injury. Fibroblast populations from the superficial and deep dermal layers of normal human skin (SN and DN, respectively) and from superficial and deep layers of hypertrophic scars (SSc and DSc, respectively) were established and cultured in serum-free medium with or without several growth 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 analyzed 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 fibroblasts but not by SSc or DSc fibroblasts. DN and DSc fibroblasts accumulated significantly more of the 24-kDa IGFBP species than SN or SSc fibroblasts in all conditions except TGF-beta or IGF-I treatment. These findings indicate that superficial and deep dermal fibroblasts are heterogeneous with respect to IGFBP release, and suggest that hypertrophic scar fibroblasts may represent a population of cells with regulatory properties distinct from those of normal dermal fibroblasts.