Genetic- or transforming growth factor-beta 1-induced changes in epidermal peroxisome proliferator-activated receptor beta/delta 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)beta/delta occupies a unique position at the intersection of diverse inflammatory or anti-inflammatory signals that influence wound repair. This study shows how changes in PPARbeta/delta expression have a profound effect on wound healing. Using two different in vivo models based on topical application of recombinant transforming growth factor (TGF)-beta1 and ablation of the Smad3 gene, we show that prolonged expression and activity of PPARbeta/delta accelerate wound closure. The results reveal a dual role of TGF-beta1 as a chemoattractant of inflammatory cells and repressor of inflammation-induced PPARbeta/delta expression. Also, they provide insight into the so far reported paradoxical effects of the application of exogenous TGF-beta1 at wound sites.
Tan
Nguan Soon
NS
Center for Integrative Genomics, National Center of Competence in Research Frontiers in Genetics, University of Lausanne, Lausanne CH-1015, Switzerland.
Michalik
Liliane
L
Desvergne
Béatrice
B
Wahli
Walter
W
D000287:Administration, Topical; D000818:Animals; D004817:Epidermis / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047494:PPAR delta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D048068:PPAR-beta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology
D047494:PPAR delta; D048068:PPAR-beta; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1