Tissue repair by thrombin-derived peptides in the rat.
An ordered sequence of events occurs following tissue damage to bring about healing. One molecule involved in this process is thrombin. Utilizing rat linear incision and full dermal excision models, we have investigated the ability of two thrombin-derived RGD-containing peptides, p517 and p508, to enhance tissue repair under normal and healing-impaired conditions. p508, at 0.5 micrograms peptide per wound, produced a significant .23% improvement in wound strength in a dose-dependent manner. Similarly, a single application of 0.5 micrograms p517 per 6-cm linear incision would significantly increased wound-breaking strength approximately 18% at nine days postsurgery (control: 3.95 +/- 0.13 Newtons, vs. p517: 4.68 +/- 0.13 Newtons; P < 0.001). However, in glucocorticoid-stressed rats, the application of 0.5 micrograms per wound p508 or 517 did not significantly influence steroid-impaired healing. In the full dermal skin excision wound model, a single application of 0.5 micrograms p508 per wound at the time of surgery significantly reduced average wound area at days 3 and 5, when healing was impaired by glucocorticoid administration. Wound area was also reduced by p508 treatment at day 3 in the normal animal, but this effect was not statistically significant. We suggest wound-healing benefits of p508 and p517 may activate wound fibroblast proliferation or stimulate other cell types in the wound site through an RGD-mediated interaction.
Warren
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Monsanto Company, St. Louis, MO 63167.
Mustoe
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Glenn
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D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012883:Skin Ulcer / Q000188:drug therapy; D013917:Thrombin / Q000494:pharmacology* / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D009842:Oligopeptides; D010446:Peptide Fragments; C047981:arginyl-glycyl-aspartic acid; D013917:Thrombin