Acceleration of soft tissue repair by a thrombin-derived oligopeptide.
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.
Cromack
D T
DT
Department of Surgery, Washington University Medical Center, St. Louis, Missouri.
Porras-Reyes
B H
BH
Wee
S S
SS
Glenn
K C
KC
Purdy
J A
JA
Carney
D H
DH
Mustoe
T A
TA
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
D010446:Peptide Fragments; C076901:thrombin receptor-activating peptide (P508-530)