The Contribution of Peroxisome Proliferator-Activated Receptor Gamma to Cutaneous Wound Healing.

SIGNIFICANCE: Cutaneous tissue repair involves an initial inflammatory phase, followed by a fibroproliferative phase and finally by a resolution phase. Failure to initiate fibroblast recruitment during the fibroproliferative phase results in chronic wounds, whereas failure to terminate the fibroproliferative phase results in fibroproliferative disorders. Thus, understanding how to regulate the fibroproliferative phase of tissue repair is, therefore, of high clinical relevance. Controlling the rate of the fibroproliferative response is essential to promote proper wound repair. RECENT ADVANCES: (1) The myofibroblast is essential for mediating the fibroproliferative phase of tissue repair. (2) The potent profibrotic cytokine transforming growth factor beta (TGF-β) is a major in vivo contributor to myofibroblast differentiation and activity in vivo. CRITICAL ISSUES: An increasing body of evidence indicates that the transcription factor peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a key in vivo role in suppressing the fibrogenic response by antagonizing TGF-β signaling. Excessive scarring and/or chronic wounds, caused by a dysregulated fibroproliferative phase, are major clinical problems in response to tissue injury. FUTURE DIRECTIONS: The development of drugs to control the rate of the fibroproliferative response are clinically relevant. Controlling PPAR-γ activity may be useful for prevention of scarring as well as for promoting the closure of chronic wounds.