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

Fiche publication


Date publication

août 2001

Journal

The Journal of cell biology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr METZGER Daniel


Tous les auteurs :
Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J, Peters JM, Kaya G, Gonzalez FJ, Zakany J, Metzger D, Chambon P, Duboule D, Wahli W

Résumé

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

Mots clés

Animals, Cell Adhesion, Cell Division, Cell Movement, Collagen, metabolism, Elastin, metabolism, Epidermis, cytology, Hair Follicle, injuries, Keratinocytes, cytology, Macrophages, cytology, Mice, Mice, Mutant Strains, Neutrophils, cytology, Peroxisomes, physiology, Receptors, Cytoplasmic and Nuclear, genetics, Skin, injuries, Tetradecanoylphorbol Acetate, pharmacology, Transcription Factors, genetics, Up-Regulation, Wound Healing, genetics

Référence

J. Cell Biol.. 2001 Aug;154(4):799-814