The Effect of an AP-1 decoy on Collagen Synthesis in Wound Healing on Rat Skin: The use of Gene Therapy to Minimise Scarring
BACKGROUND: The wound healing process is composed of inflammation, cellular growth, migration, angiogenesis and an extracellular matrix composition. In this process, fibroblasts proliferate but leave scarring due to their excessive growth. The process is controlled by platelet derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), while PDGF and transforming growth factor beta(TGF-beta) play a major role in controlling extracellular matrix composition. Numerous modalities have been tried to treat this abnormal response, but the results were unsatisfactory. TGF-beta is activated by AP-1 (Activator protein). Theregone, AP-1 decoy oligodeoxynucleotides(ODN) had recently been used for regulation of TGF-beta transcription as a gene treatment. OBJECTIVE: The purpose of this study was to examine the effect of blocking TGF-beta transcription by an AP-1 decoy ODN on collagen synthesis in wound healing on rat skin. METHODS: In this study, the effect of AP-1 decoy ODN on collagen synthesis was examined by Hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and immunohistochemical staining for TGF-beta on damaged rat skin. RESULTS: In the H&E stain and Masson's trichrome stain of the damaged rat skin, the number of collagen fibers of AP-1 decoy ODN treated group had decreased in compared to the control group, especially on the 15th day after incision. With immunohistochemical stain, the expression of TGF-beta in fibroblasts, inflammatory cells and the endothelium of vessel walls in the dermis had also decreased, compared to the control group. TGF-beta was expressed in the dermis from the 3rd day, and predominantly in the fibroblasts on the 15th day after incision. CONCLUSION: These results indicate that AP-1 decoy ODN is a powerful down-regulator of collagen synthesis in wound healing through significant suppression of TGF-beta expression in damaged skin. Therefore, AP-1 decoy ODN can be used effectively to treat or minimize scarring on damaged skin.
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