成纤维细胞(FB)活化增殖是口腔黏膜下纤维性变(OSF)发病的重要环节。时钟基因DEC1参与了细胞增殖、凋亡、分化、EMT等多种生理病理过程。本课题组前期研究表明：DEC1在OSF中表达上调并促进了FB活化增殖，其表达与FAK-PI3K/Akt通路活化有关。据此并结合文献，我们提出：DEC1在OSF中调控FAK激活PI3K/Akt促进FB活化增殖。本项目拟利用已构建好的DEC1基因敲除OSF小鼠模型、OSF组织标本及成纤维细胞等①免疫组化验证DEC1、FAK、PI3K在OSF中的作用；②体外研究DEC1-FAK-PI3K/Akt促进FB活化增殖的级联通路；③探究DEC1促进FAK磷酸化的具体分子机制；④在已构建好的DEC1基因敲除OSF小鼠模型中探索DEC1作为靶标治疗OSF的可行性。本项目的实施有望为补充OSF发病新机制、找寻药物治疗新靶标提供基础。

The activation and proliferation of fibroblast(FB) are important links in the pathogenesis of oral submucous fibrosis(OSF). The clock gene DEC1 plays an important role in various diseases of human body, but there is no report in fibrotic diseases. Our previous studies have shown that the up-regulated DEC1 is positively related to the activation of FAK and PI3K, and the up-regulation of DEC1 promotes the activation and proliferation of FB, suggesting that DEC1 might play a role in OSF. Based on these studies, we think that DEC1 promotes the activation and proliferation of FB by regulating FAK which further activates PI3K/Akt. This project intends to use the established OSF model in DEC1 gene knockout mice, OSF specimens and fibroblast to ①verify the role of DEC1, FAK, PI3K in OSF ②study the molecular mechanism of promoting the activation and proliferation of FB by DEC1-FAK-PI3K/Akt cascade pathway ③explore the regulatory mechanism of DEC1 in promoting the phosphorylation of FAK ④further verify the role of DEC1-FAK-PI3K/Akt cascade pathway in promoting the activation and proliferation of FB.