Genetic- or transforming growth factor-β1-induced changes in epidermal peroxisome proliferator-activated receptor β/δ expression dictate wound repair kinetics

Advances in wound care are of great importance in clinical injury management. In this respect, the nuclear receptor peroxisome proliferator-activated receptor (PPAR)β/δ occupies a unique position at the intersection of diverse inflammatory or anti-inflammatory signals that influence wound repair. This study shows how changes in PPARβ/δ expression have a profound effect on wound healing. Using two different in vivo models based on topical application of recombinant transforming growth factor (TGF)-β1 and ablation of the Smad3 gene, we show that prolonged expression and activity of PPARβ/δ accelerate wound closure. The results reveal a dual role of TGF-β1 as a chemoattractant of inflammatory cells and repressor of inflammation-induced PPARβ/δ expression. Also, they provide insight into the so far reported paradoxical effects of the application of exogenous TGF-β1 at wound sites.