Microarray and Immunohistochemical Characterization of Silicone Gel Occlusion in a Novel Murine Cutaneous Wound Model (Recipient of the Young Investigator's Award at the 2007 Wound Healing Society Meeting)

摘要

The efficacy of silicone gel occlusion in the treatment of hypertrophic scarring has been well documented. In vitro evidence has been reported suggesting that this effect is mediated through normalization of epidermal hydration and a concomitant attenuation of epidermal activation. Activated keratinocytes are characterized by altered patterns of keratin expression, cytokine and growth factor signaling. In an attempt to study this phenomenon in vivo, we have established a novel murine cutaneous wound model which accurately recapitulates the proliferation of epidermal keratinocytes and altered spectrum of cytokeratin expression consistent with the activated keratinocyte phenotype. Introduction of silicone gel occlusion in our model results in attenuation of keratinocyte activation as well as modulation of cytokine and growth factor signaling pathways suggesting accelerated restoration of the basal keratinocyte phenotype. We observe that occlusion results in a marked downregulation of keratin-6 expression(a marker of keratinocyte activation) and a decrease in JAK/STAT dependant cytokine signaling activity. Conversely, occlusion appears to accelerate the TGF-beta mediated restoration of the basal keratinocyte phenotype.