Increased wound-breaking strength induced by insulin-like growth factor I in combination with insulin-like growth factor binding protein-1.
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.
Jyung
R W
RW
Division of Plastic Surgery, Washington University School of Medicine, St. Louis, Mo.
Mustoe
J A
JA
Busby
W H
WH
Clemmons
D R
DR
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D006909:Hydroxyproline / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D006909:Hydroxyproline