Li Jun, Li Ping, Zhang Yan, Li Gong-Bo, He Feng-Tian, Zhou Yuan-Guo, Yang Kang, Dai Shuang-Shuang
Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Cell Physiol Biochem. 2012;30(4):1059-71. doi: 10.1159/000341482. Epub 2012 Sep 24.
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.
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.
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.
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.
背景/目的：研究过氧化物酶体增殖物激活受体（PPAR）δ与Ski的相互作用以及这种相互作用在伤口愈合中的相关效应。
通过实时PCR和蛋白质印迹法检测PPARδ激活对大鼠皮肤成纤维细胞中Ski表达的影响。进行荧光素酶报告基因检测、电泳迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）分析，以鉴定大鼠Ski基因启动子区域中PPARδ的结合位点。并在成纤维细胞增殖和大鼠皮肤伤口愈合模型中检测PPARδ对Ski调控的功能活性。
PPARδ激动剂GW501516以剂量依赖性方式上调Ski表达。位于Ski启动子区域-865∼-853处的直接重复序列1（DR1）反应元件被鉴定为介导PPARδ与Ski结合及相关的Ski诱导。此外，PPARδ上调Ski以促进成纤维细胞增殖和大鼠皮肤伤口修复，而Ski RNA干扰预处理可在很大程度上阻断这种作用。
本研究表明Ski是PPARδ的一个新靶基因，PPARδ介导的伤口愈合与上调Ski促进成纤维细胞增殖有关。
