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

Abstract

Background/Aim: Both peroxisome proliferator-activated receptor (PPAR) δ and Ski are investigate the interaction of PPARδ and Ski and this interaction-associated effect in wound healing. Methods: Effect of PPARδ 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 PPARδ in the promoter region of rat Ski gene. And the functional activity of PPARδ regulation to Ski was detected in fibroblast proliferation and rat skin wound healing model. Results: PPARδ agonist GW501516 upregulated Ski expression in a dose-dependent manner. Direct repeat-1 (DR1) response element locating at -865∼-853 in Ski promoter region was identified to mediate PPARδ binding to Ski and associated induction of Ski. Furthermore, PPARδ 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 PPARδ and upregulation of Ski to promote fibroblast proliferation is implicated in the PPARδ-mediated wound healing.