Roles of the peroxisome proliferator-activated receptor (PPAR) α and β/δ in skin wound healing

The peroxisome proliferator-activated receptors (PPARxα, PPARβ/δ, called PPARβ below, and PPARγ) are ligand-activated transcription factors. They belong to the nuclear hormone receptor superfamily and are sensors of physiological levels of fatty acids and fatty acid derivatives. In the healthy skin of adult mice, they are expressed at very low levels in interfollicular epidermis keratinocytes, and are found at high levels in hair follicle keratinocytes. After a skin injury, the expression of PPARα and PPARβ is stimulated at the site of the wound. A detailed analysis of PPARβ revealed a spatiotemporal control program that first stimulates PPARβ expression immediately after the injury. Second, as the wound heals, this expression is gradually repressed to reach background levels after completion of wound closure. This regulation depends on opposite effects of TNF-α, which stimulates, and TGF-β1, which down-regulates the activity of the PPARβ gene.