Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPAR beta mutant mice

We show here that the alpha, beta, and gamma isotypes of peroxisome prolife rator-activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfoll icular epithelium after birth. Interestingly, PPAR alpha and beta expressio n is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbo l acetate topical application, hair plucking, or skin wound healing. Using PPAR alpha, beta, and gamma mutant mice, we demonstrate that PPAR alpha and beta are important for the rapid epithelialization of a skin wound and tha t each of them plays a specific role in this process. PPAR alpha is mainly involved in the early inflammation phase of the healing, whereas PPAR beta is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPAR beta mutant primary keratinocytes show impaired a dhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPAR alpha and beta in adult mouse epidermal repair.