Peroxisome proliferator-activated receptor (PPAR)-beta as a target for wound healing drugs: what is possible?

Détails

ID Serval
serval:BIB_8E89E274F7A5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peroxisome proliferator-activated receptor (PPAR)-beta as a target for wound healing drugs: what is possible?
Périodique
American Journal of Clinical Dermatology
Auteur(s)
Tan N.S., Michalik L., Desvergne B., Wahli W.
ISSN
1175-0561[print], 1175-0561[linking]
Statut éditorial
Publié
Date de publication
2003
Volume
4
Numéro
8
Pages
523-530
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
Publication Status: ppublish
Résumé
Peroxisome proliferator-activated receptor (PPAR) dysfunction has been implicated in the manifestation of many diseases and illnesses, ranging from obesity to cancer. Herein, we discuss the role of PPARbeta, one of the three PPAR isotypes, during wound healing. While PPARbeta expression is undetectable in unchallenged and healthy adult interfollicular mouse skin, it is robustly re-activated in stress situations, such as upon phorbol ester treatment, hair plucking and cutaneous wounding. The inflammatory reaction associated with a skin injury activates the keratinocytes at the edges of the wound. This activation involves PPARbeta, whose expression and activity as transcription factor are up-regulated by pro-inflammatory signals. The re-activation of PPARbeta influences three important properties of the activated keratinocytes that are vital for rapid wound closure, namely, survival, migration and differentiation. The anti-apoptotic and, thus, survival role of PPARbeta is mediated by the up-regulation of expression of integrin-linked kinase and 3-phosphoinositide-dependent kinase-1. Both kinases are required for the full activation of the Akt1 survival cascade. Therefore, the up-regulation of PPARbeta, early after injury, appears to be important to maintain a sufficient number of viable keratinocytes at the wound edge. At a later stage of wound repair, the stimulation of keratinocyte migration and differentiation by PPARbeta is also likely to be important for the formation of a new epidermis at the wounded area. Consistent with these observations, the entire wound healing process is delayed in PPARbeta +/- mice and wound closure is retarded by 2-3 days. The multiple roles of PPARbeta in the complex keratinocyte response after injury and during skin repair certainly justify a further exploration of its potential as a target for wound healing drugs.
Mots-clé
Animals, Cell Movement, Keratinocytes/physiology, Mice, Receptors, Cytoplasmic and Nuclear/drug effects, Receptors, Cytoplasmic and Nuclear/physiology, Skin/injuries, Transcription Factors/drug effects, Transcription Factors/physiology, Wound Healing/drug effects, Zinc Fingers/drug effects
Pubmed
Web of science
Création de la notice
24/01/2008 16:26
Dernière modification de la notice
03/03/2018 19:18
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