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Increased wound-breaking strength induced by insulin-like growth factor I in combination with insulin-like growth
R W Jyung1, J A Mustoe, W H Busby
1Division of Plastic Surgery, Washington University School of Medicine, St. Louis, Mo.
Background:
Polypeptide growth factors have been shown to accelerate wound repair in rodent animal model systems.
Methods:
In this report, insulin-like growth factor I (IGF-I) and the combination of IGF-I plus insulin-like growth factor binding protein (IGFBP-1) were applied directly to linear incisions made through dorsal rat skin, and histologic analysis of breaking strength and hydroxyproline quantification were performed.
Results:
IGF-I alone, in contrast to transforming growth factor-beta and platelet-derived growth factor, had no effect on wound-breaking strength. However, the combination of IGF-I plus IGFBP-1 significantly increased wound-breaking strength. Wound-breaking strength was increased 33% compared with wounds treated with IGF-I alone. IGFBP-1 alone had no effect. The ability to stimulate breaking strength was dependent on posttranslation modification of IGFBP-1. Phosphorylated IGFBP-1 was without effect, whereas the dephosphorylated protein was fully biologically active. This increase in wound-breaking strength induced by the combination of IGF-I and dephosphorylated IGFBP-1 was accompanied by an 67% increase in wound hydroxyproline content, whereas the combination of IGF-I and the phosphorylated form of IGFBP-1 had no effect.
Conclusions:
We concluded that IGF-I is a potent stimulant of incisional wound healing, but if administered without other growth factors, its effects can only be shown when it is combined with one of its specific binding proteins.