PAK1信号通路影响Foxp3表达在银屑病致病机制中的研究

Based on literature, P21-activated kinase (PAK1) signal pathway has key roles in cell survival, cell proliferation, cell migration and inflammation; The forkhead box protein 3 (Foxp3) has immunosuppressive capacity by functionally and numerically regulating of Regulatory T-cells. According to our previous study, it has been proved by immunohistochemistry and Western blotting that the p-PAK1 is overexpressed in psoriatic lesions and participated proliferation of keratinocytes. The current literature mentioned Foxp3 is abnormally expressed in psoriatic lesions, however, the correlation of PAK1 and Foxp3 level in CD4+CD25+T cells in keratinocyte proliferation and inflammation response of psoriasis is not clear, therefore the aim of this study is to illustrate how PAK1 and Foxp3 participate in keratinocyte proliferation and inflammation in psoraisis. To my best knowledge, this study proposed first time that PAK1 signal pathway plays key role in on bionomics of keratinocyte and inflammation response of psoriasis by regulating Foxp3.

基于文献：PAK1是涉及细胞增殖、肿瘤、免疫性疾病、炎症的重要信号通路；FOXP3主要通过影响CD4+CD25+ T细胞数量及功能，从而发挥免疫抑制功能，最终导致机体免疫失衡。在前期研究工作中，通过免疫组织化学、WesternBlotting从不同角度证实了PAK1信号通路在银屑病皮损中过度活化，且与角质形成细胞的增殖和凋亡相关；目前文献提示Foxp3在银屑病皮损中异常表达，但关于PAK1信号通路及Foxp3在调控银屑病角质形成细胞增殖和炎症反应中的相互作用机制尚不清楚。本项目拟通过基因转染技术诱导或阻断角质形成细胞PAK1信号通路，研究角质形成细胞增殖凋亡情况，并探索PAK1与Foxp3在银屑病局部炎症形成中的相互作用机制。本课题首次提出关于PAK1信号通路对角质形成细胞生物学行为的影响及其通过Foxp3影响银屑病局部炎症微环境的作用探讨。