Peroxisome proliferator-activated receptor-beta as a target for wound healing drugs.
Healing of cutaneous wounds, which is crucial for survival after an injury, proceeds via a well-tuned pattern of events including inflammation, re-epithelialisation, and matrix and tissue remodelling. These events are regulated spatio-temporally by a variety of growth factors and cytokines. The inflammation that immediately follows injury increases the expression of peroxisome proliferator-activated receptor (PPAR)-beta in the wound edge keratinocytes and triggers the production of endogenous PPARbeta ligands that activate the newly produced receptor. This elevated PPARbeta activity results in increased resistance of the keratinocytes to the apoptotic signals released during wounding, allowing faster re-epithelialisation. The authors speculate that, in parallel, ligand activation of PPARbeta in infiltrated macrophages attenuates the inflammatory response, which also promotes repair. Thus, current understanding of the roles of PPARbeta in different cell types implicated in tissue repair has revealed an intriguing intercellular cross-talk that coordinates, spatially and temporally, inflammation, keratinocyte survival, proliferation and migration, which are all essential for efficient wound repair. These novel insights into the orchestrating roles of PPARbeta during wound healing may be helpful in the development of drugs for acute and chronic wound disorders.
Tan
Nguan Soon
NS
Center for Integrative Genomics, NNCR Frontiers in Genetics, University of Lausanne, Switzerland.
Michalik
Liliane
L
Desvergne
Béatrice
B
Wahli
Walter
W
D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007249:Inflammation; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D048068:PPAR-beta / Q000819:agonists* / Q000502:physiology; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism; D012867:Skin / Q000293:injuries; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D016207:Cytokines; D006133:Growth Substances; D048068:PPAR-beta