Loss of PPARγ expression by fibroblasts enhances dermal wound closure
1 Department of Dentistry, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Bldg., London, ON, N6A 5C1, Canada
2 Department of Rheumatology, Jewish General Hospital, 3755 Cote St. Catherine Rd., Montreal, QC, H3T 1E2, Canada
3 Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Bldg., London, ON, N6A 5C1, Canada
Fibrogenesis & Tissue Repair 2012, 5:5 doi:10.1186/1755-1536-5-5Published: 13 April 2012
Peroxisome proliferator-activated receptor (PPAR)γ may be a key regulator of connective tissue deposition and remodeling in vivo. PPARγ expression is reduced in dermal fibroblasts isolated from fibrotic areas of scleroderma patients; PPARγ agonists suppress the persistent fibrotic phenotype of this cell type. Previously, we showed that loss of PPARγ expression in fibroblasts resulted in enhanced bleomycin-induced skin fibrosis. However, whether loss of PPARγ expression in skin fibroblasts affects cutaneous tissue repair or homeostasis is unknown.
Mice deleted for PPARγ 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, α-smooth muscle actin (α-SMA) and CCN2. Conversely, dermal homeostasis was not appreciably affected by loss of PPARγ expression.
PPARγ expression by fibroblasts suppresses cutaneous tissue repair. In the future, direct PPARγ antagonists and agonists might be of clinical benefit in controlling chronic wounds or scarring, respectively.