Upregulation of Ski in Fibroblast is Implicated in the Peroxisome Proliferator-Activated Receptor δ-Mediated Wound Healing

Background/Aim: Both peroxisome proliferator-activated receptor (PPAR) delta and Ski are reported to be involved in skin wound repair. However, their link is unclear. Our aim is to investigate the interaction of PPAR delta and Ski and this interaction-associated effect in wound healing. Methods: Effect of PPAR delta activation on Ski expression was detected in rat skin fibroblasts by real-time PCR and western blot. Luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were performed to identify the binding site of PPAR delta in the promoter region of rat Ski gene. And the functional activity of PPAR delta regulation to Ski was detected in fibroblast proliferation and rat skin wound healing model. Results: PPAR delta agonist GW501516 upregulated Ski expression in a dose-dependent manner. Direct repeat-1 (DR1) response element locating at -865 similar to-853 in Ski promoter region was identified to mediate PPAR delta binding to Ski and associated induction of Ski. Furthermore, PPAR delta upregulated Ski to promote fibroblasts proliferation and rat skin wound repair, which could be largely blocked by pre-treated with Ski RNA interference. Conclusion: This study demonstrates that Ski is a novel target gene for PPAR delta and upregulation of Ski to promote fibroblast proliferation is implicated in the PPAR delta-mediated wound healing. Copyright (C) 2012 S. Karger AG, Basel