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.
This work was supported by grants from the Swiss National Science Foundation (to W. W. and B. D.) and the Etat de Vaud. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains Figs. S1–S6.
