Loss of PPAR gamma expression by fibroblasts enhances dermal wound closure

Background: Peroxisome proliferator-activated receptor (PPAR)gamma may be a key regulator of connective tissue deposition and remodeling in vivo. PPAR gamma expression is reduced in dermal fibroblasts isolated from fibrotic areas of scleroderma patients; PPAR gamma agonists suppress the persistent fibrotic phenotype of this cell type. Previously, we showed that loss of PPAR gamma expression in fibroblasts resulted in enhanced bleomycin-induced skin fibrosis. However, whether loss of PPAR gamma expression in skin fibroblasts affects cutaneous tissue repair or homeostasis is unknown. Results: Mice deleted for PPAR gamma in skin fibroblasts show an enhanced rate of dermal wound closure, concomitant with elevated phosphorylation of Smad3, Akt and ERK, and increased expression of proliferating cell nuclear antigen (PCNA), collagen, alpha smooth muscle actin (alpha SMA) and CCN2. Conversely, dermal homeostasis was not appreciably affected by loss of PPAR gamma expression. Conclusion: PPAR gamma expression by fibroblasts suppresses cutaneous tissue repair. In the future, direct PPAR gamma antagonists and agonists might be of clinical benefit in controlling chronic wounds or scarring, respectively.