The Effect Of Topical Application Of PPAR β/δAgonist GW0742on HSF-1Expression And Healing Rate In The Mouse Skin Wound

Objective:To investigate whether the topical application of GW0742,an agonist of PPAR β could affect the expression of HSF-1in the keratinocyte and fibroblast cells on the wound bed of a full-thickness skin defect mouse model.Material and method:We made a mouse model with dorsal full-thickness skin excision and evaluated the healing rate. Two equal skin excisions were made beside the backbone of each mouse, one side treated by GW0742while the other side applied with saline, wound area were calculated by transparency films on day of1d、3d、7d、14d、21d after operation, the healing rates were compared between two groups. The biopsy of wound edge were collected on day of0d、1d、7d、14d、21d after operation, expression of HSF-1、PPAR β were analyzed and compared.Results:Healing rates between two groups show little differences, while in the process of healing, wounds treated by GW0742show less inflammatory cells infiltration, and demonstrated better keratinization in the latter stage of healing. The expression of PPAR β were up regulated after incision and it reach to the maximum on the7th-14th days, compared to the control group, application of GW0742up regulating PPAR β distinctly, What’s more, the maximum expression phase of PPAR β was prolonged by GW042. The expression of HSF-1were also up regulated instantly in the skin after injury, and reach to the maximum by the14th day after excision. In the earlier stage of healing (1-7days after operation), HSF-1were located mainly in the cytoplasm of epidermal cells in the follicles and glandular cells in sweet gland. As granulation tissue and new epidermis formed (7-21d after operation), expression of HSF-1mainly located in the nucleus of fibroblast cells, compare to the control group, external use of GW0742activated HSF-1and promote its nucleus translocation apparently(p<0.05), while at the end of healing process, the expression of HSF-1show little difference between two groups(p>0.05).Conclusion:1. Topical application of GW0742stimulate PPAR β expression in fibroblast cells on the wound bed, maximum phase of PPAR β also been prolonged.2. The expression and activity of HSF-1in the fibroblast on wound bed also been up regulated by topical using of GW0742, which can be proved by much more translocated HSF-1were found on the experimental group wound bed.3. Even though we were failure on demonstrating GW0742accelerating the healing rate of the skin wound, topical using of GW0742still moderates the inflammatory response on the wound bed by reducing the infiltrate of the inflammatory cells, what’s more, keratinization of the new formed skin were much better in the experimental group.