Role of TGFβ-mediated inflammation in cutaneous wound healing

Abstract

Among many molecules known to influence wound healing, transforming growth factor β1 (TGFβ1) has the broadest spectrum of actions, affecting all cell types that are involved in all stages of wound healing. Both positive and negative effects of TGFβ1 on wound healing have been reported. However, the underlying mechanisms are largely unknown. We observed that endogenous TGFβ1 was elevated in a narrow window of time after injury, and transgenic mice constitutively overexpressing wild-type TGFβ1 in keratinocytes (K5.TGFβ1wt) exhibited a significant delay in full-thickness wound healing as compared to non-transgenic mice. Delayed wound healing was associated with profound inflammation throughout all stages of wound healing in K5.TGFβ1wt mice. Our data suggest that excessive and prolonged TGFβ1 at the wound site does not benefit wound healing, which is partially owing to its pro-inflammatory effect. Future studies need to be conducted to assess whether tightly regulated TGFβ1 expression will benefit wound healing. To this end, we have developed a gene-switch TGFβ1 transgenic system that allows TGFβ1 induction in keratinocytes temporally with desired levels. These mice will provide a tool to study stage-specific effects of TGFβ1 on cutaneous wound healing. © 2006 The Society for Investigative Dermatology.