Syndecan-1 expression is enhanced in cutaneous and mucosal wounds. We have previously demonstrated that wounding-induced syndecan-1 expression in the skin occurs transcriptionally, through a fibroblast-growth-factor-inducible element (FiRE). Here, we show that FiRE is also activated in mucosal wounds. However, both the expression patterns and the activation mechanisms of FiRE are different from those in the skin. In the mucosa in vivo, the activation starts and ends earlier than in cutaneous wounds. FiRE is first detected at around 12 hours in keratinocytes, and the activation declines by the third day after wounding occurs. The activation is seen on the migrating sheet of epithelial mucosa, as in the case of cutaneous wounding. In contrast to the situation in vivo, organ-cultured mucosal wounds exhibit no FiRE activity, while organ-cultured cutaneous wounds show robust activity. Activation in mucosal wounds is enhanced, however, by the application of epidermal growth factor. This suggests that exogenous growth factor activity is required for activation of syndecan-1 in mucosal wounds but not in cutaneous wounds.