RESUMO
The role of polypeptide growth factors in the processes of inflammation and repair was investigated by analyzing the influence of transforming growth factor-beta (TGF-beta), applied directly to linear incisions made through rat dorsal skin. A dose-dependent, direct stimulatory effect of a single application of TGF-beta on the breaking strength of healing incisional wounds was demonstrated. An increase in maximum wound strength of 220 percent of control was observed at 5 days; the healing rate was accelerated by approximately 3 days for at least 14 days after production of the wound and application of TGF-beta. These increases in wound strength were accompanied by an increased influx of mononuclear cells and fibroblasts and by marked increases in collagen deposition at the site of application of TGF-beta. TGF-beta is thus a potent pharmacologic agent that can accelerate wound healing in rats.
Assuntos
Substâncias de Crescimento/farmacologia , Peptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Ferimentos Penetrantes/patologia , Animais , Masculino , Ratos , Ratos Endogâmicos , Coloração e Rotulagem , Fatores de Crescimento TransformadoresRESUMO
This study examined the potential influence of platelet-derived growth factor-BB homodimers (PDGF-BB) on surgical incisions in irradiated animals with depressed wound healing. Rats were irradiated with either 800 rads total body or 2,500 rads surface irradiation. Parallel dorsal skin incisions were made 2 days later, and PDGF-BB was applied topically a single time to one of two incisions. In total body-irradiated rats, bone marrow-derived elements were severely depressed, wound macrophages were virtually eliminated, and PDGF-BB treatment was ineffective. However, in surface-irradiated rats, PDGF-BB treatment recruited macrophages into wounds and partially reversed impaired healing on day 7 (p less than 0.005) and day 12 (p less than 0.001). PDGF-BB-treated wounds were 50 percent stronger than the paired control wounds. The results suggest PDGF requires bone marrow-derived cells, likely wound macrophages, for activity and that it may be useful as a topical agent in postirradiation surgical incisions.
Assuntos
Fator de Crescimento Derivado de Plaquetas/uso terapêutico , Radioterapia de Alta Energia/efeitos adversos , Cicatrização/efeitos da radiação , Animais , Medula Óssea/efeitos da radiação , Relação Dose-Resposta a Droga , Fibroblastos/fisiologia , Macrófagos/efeitos da radiação , Masculino , Ratos , Ratos Endogâmicos , Pele/efeitos da radiação , Irradiação Corporal Total/efeitos adversosRESUMO
Platelet-derived growth factor-BB has multiple effects in vitro and has been demonstrated to accelerate wound healing in several animal models, but its precise mechanisms of action in vivo have not been fully explained. A rat mesentery culture model was developed, and platelet-derived growth factor-BB (100 ng/ml) was added to the medium containing 2% fetal calf serum for examining its closure effects. The mesentery specimens were stained by routine hematoxylin and eosin and immunohistochemical staining for macrophages. A significant improvement in closure rate and complete closure rate was seen when platelet-derived growth factor-BB was added to the medium compared with the controls (p < 0.05). There are significantly fewer macrophages in the in vitro specimen than in the in vivo specimen. In conclusion, platelet-derived growth factor-BB can contribute to wound closure of a mesenteric defect even without macrophages, suggesting a second mechanism in which it can act directly on mesenchymal cells during wound healing. This tissue-culture model is useful for gaining further insights into growth factor interactions and wound healing.
Assuntos
Macrófagos/fisiologia , Mesentério/lesões , Fator de Crescimento Derivado de Plaquetas/farmacologia , Cicatrização/fisiologia , Animais , Becaplermina , Meios de Cultura , Técnicas de Cultura , Masculino , Proteínas Proto-Oncogênicas c-sis , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Cicatrização/efeitos dos fármacosRESUMO
Transforming growth factor beta (TGF-beta) and the platelet-derived growth factor (PDGF) are potent mitogenic polypeptides which enhance rates of wound healing in experimental animals; in contrast, glucocorticoids inhibit wound repair. The potential of TGF-beta and PDGF to reverse this inhibition in healing was tested in methylprednisolone-treated rats with deficits in skin wound strength of 50%. Single applications of TGF-beta (10-40 pmol per wound, 0.25-1 micrograms) applied locally at the time of wounding fully reversed this deficit in a concentration-dependent and highly reproducible manner. Wounds in glucocorticoid-treated animals were characterized by a near total absence of neutrophils and macrophages and by a delayed influx and reduced density of fibroblasts; however, such wounds treated with TGF-beta showed significant increases in wound fibroblasts and in intracellular procollagen type I. PDGF did not reverse the deficit in wound breaking strength in glucocorticoid-treated rats; there were more fibroblasts in the PDGF-treated wounds, but these fibroblasts lacked the enhanced expression of procollagen type I found in TGF-beta-treated wounds. The wound macrophages, required for normal tissue repair, remained absent from both PDGF- and TGF-beta-treated wounds in glucocorticoid-treated animals. This result suggested that macrophages might normally act as an intermediate in the induction of procollagen synthesis in fibroblasts of PDGF-treated wounds and that TGF-beta might bypass the macrophage through its capacity to stimulate directly new synthesis of procollagen type I in fibroblasts. Whereas PDGF does not stimulate procollagen synthesis, in a rodent macrophage cell line, PDGF induced a highly significant, time-dependent enhancement of expression of TGF-beta.