Glucocorticoid-regulated gene expression during cutaneous wound repair.
Glucocorticoids exert a deleterious effect on the wound healing process, which has been suggested to result from the anti-inflammatory action of these steroids. In addition, recent studies have demonstrated that glucocorticoids regulate the expression of various genes at the wound site which are likely to encode key players in the wound repair process. Using a murine full-thickness excisional wound healing model, we analyzed the effect of dexamethasone on the expression of various cytokines, growth factors, enzymes, and extracellular matrix molecules in normal and wounded skin. We demonstrate that the proinflammatory cytokines interleukin-1 alpha and -beta, tumor necrosis factor alpha, keratinocyte growth factor, transforming growth factors beta 1, beta 2, and beta 3 and their receptors, platelet-derived growth factors and their receptors, tenascin-C, stromelysin-2, macrophage metalloelastase, and enzymes involved in the generation of nitric oxide are targets of glucocorticoid action in wounded skin. These results indicate that anti-inflammatory steroids inhibit wound repair at least in part by influencing the expression of these key regulatory molecules.
Beer
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HD
Institute of Cell Biology, ETH-Hönggerberg, Zürich, Switzerland.
Fässler
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R
Werner
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D000818:Animals; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000009:adverse effects*; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D016207:Cytokines; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D005938:Glucocorticoids; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D003907:Dexamethasone; D003094:Collagen; D019001:Nitric Oxide Synthase