title: Acceleration of soft tissue repair by a thrombin-derived oligopeptide.
abstract: Augmentation of thrombin-modulated chemotaxis and mitogenic activity within the early phase of soft tissue repair is now possible. Identification of high-affinity thrombin receptor binding domains within thrombin has enabled the synthesis of a family of peptides which interact with thrombin receptors and enhance in vitro mitogenesis. A single (5.0 micrograms/wound) application of the thrombin receptor-activating peptide (P517-30) significantly increased wound breaking strength from Day 5 (31% over controls) to Day 12. Two models of impaired healing created by radiotherapy (RT) were used to elucidate possible mechanisms of P517-30 action. Although P517-30 did not completely overcome the RT-induced healing impairments, it increased breaking strength under conditions of penetrating whole body RT-induced pancytopenia by 22% and of nonpenetrating surface RT-induced dermal cell damage by 42%. This suggests that P517-30 directly stimulates resident endothelial cells, fibroblasts, or other cells to overcome dermal and circulating monocytic deficits. These results suggest a method to accelerate wound healing with potential clinical applications and emphasize the activity of thrombin as a growth factor.
authors.affiliation: Department of Surgery, Washington University Medical Center, St. Louis, Missouri.
authors.forename: D T
authors.initials: DT
authors.lastname: Cromack
authors.forename: B H
authors.initials: BH
authors.lastname: Porras-Reyes
authors.forename: S S
authors.initials: SS
authors.lastname: Wee
authors.forename: K C
authors.initials: KC
authors.lastname: Glenn
authors.forename: J A
authors.initials: JA
authors.lastname: Purdy
authors.forename: D H
authors.initials: DH
authors.lastname: Carney
authors.forename: T A
authors.initials: TA
authors.lastname: Mustoe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D010446:Peptide Fragments; C076901:thrombin receptor-activating peptide (P508-530)