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.
Wang
Xiao-Jing
XJ
Department of Otolaryngology, Oregon Health & Science University, Portland, Oregon 97239, USA. wangxiao@ohsu.edu
Han
Gangwen
G
Owens
Philip
P
Siddiqui
Yasmin
Y
Li
Allen Guanqun
AG
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D015603:Keratinocytes / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000293:injuries*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000502:physiology*
C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1