Role of TGF beta-mediated inflammation in cutaneous wound healing.

Among many molecules known to influence wound healing, transforming growth factor beta 1 (TGF beta 1) 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 TGF beta 1 on wound healing have been reported. However, the underlying mechanisms are largely unknown. We observed that endogenous TGF beta 1 was elevated in a narrow window of time after injury, and transgenic mice constitutively overexpressing wild-type TGF beta 1 in keratinocytes (K5.TGF beta 1wt) 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.TGF beta 1wt mice. Our data suggest that excessive and prolonged TGF beta 1 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 TGF beta 1 expression will benefit wound healing. To this end, we have developed a gene-switch TGF beta 1 transgenic system that allows TGF beta 1 induction in keratinocytes temporally with desired levels. These mice will provide a tool to study stage-specific effects of TGF beta 1 on cutaneous wound healing.