Yes相关蛋白在银屑病表皮异常增殖及炎症浸润中的作用机制

With a high morbidity, the pathogenesis of psoriasis remains unclear and effective therapeuties are still lacking. Previous studies showed that the pathogenesis of psoriasis was closely related to RASSF. Our studies found that the expression of Yes-associated protein (YAP), a downstream protein of RASSF, was decreased in psoriasis, and YAP could inhibit the proliferation of KC, but the mechanism remains unclear. This study aims to: 1.Stimulate the cutured KC, CD8+T cells and Th17 cells from human peripheral blood by YAP and/or RASSF, then detect the alterations of the cell proliferation and inflammatory cytokines in the supernatant, and investigate its function on cell proliferation and inflammatary cytokine secretion and the relationship between them; 2. To verify the expression of YAP and RASSF and the effects on cell proliferation and the expression of inflammatory cytokines of the above cells in imiquimod psoriatic mouse models. In addition, detect the specific pathways by which YAP inhibits the KC proliferation, chemoattracts the inflammatory cells and promotes the secretion of inflammatory cytokines; 3. To verify the function of constructed overexpression vector of YAP and RASSF and siRNA interference in above cells and mouse models, and detect the mechanism and pathways in these cells and mice models. This study will reveal the critical roles of YAP in abnormal epidermal proliferation of KC and regulation of inflammatary cell differentiation, and thus provides experimental evidence and new targets for the treatment of psoriasis.

银屑病发病率高，机制不清且疗效不佳。研究表明, RASSF与银屑病的发病密切相关。我们发现，作为RASSF的下游蛋白，Yes相关蛋白（YAP）在银屑病中表达降低，其可抑制KC的增殖，但作用机制不清。本项目拟：1.用YAP和/或RASSF刺激培养的KC、外周血CD8+T细胞和Th17细胞，检测细胞的增殖状况、上清液中炎症因子的表达，探讨其对细胞增殖及炎症因子分泌的作用及两者间的关系；2.利用咪喹莫特银屑病鼠模型，检测在鼠组织和细胞中YAP和RASSF的表达，验证其在上述细胞的增殖及炎症因子分泌中的作用，进而检测YAP发挥其抑制KC的增殖，趋化炎症细胞和分泌炎性因子等作用的具体的路径；3.构建过表达的YAP和/或RASSF载体或siRNA干扰，验证其在以上细胞及鼠模型细胞中的作用机制及其路径。本课题将揭示YAP在表皮KC异常增殖和炎症细胞分化中的关键作用机制，为寻找新的治疗靶点提供实验依据。

银屑病发病率高，机制不清且疗效不佳。研究表明, RASSF与银屑病的发病密切相关。我们发现，作为RASSF的下游蛋白，Yes相关蛋白（YAP）在银屑病中表达降低，其可抑制KC的增殖，但作用机制不清。本项目通过：1.用YAP和/或RASSF刺激培养的KC、外周血CD8+T细胞和Th17细胞，检测细胞的增殖状况、上清液中炎症因子的表达，探讨了其对细胞增殖及炎症因子分泌的作用及两者间的关系；2.利用咪喹莫特银屑病鼠模型，检测在鼠组织和细胞中YAP和RASSF的表达，验其在上述细胞的增殖及炎症因子分泌中的作用，进而探究了YAP发挥其抑制KC的增殖，趋化炎症细胞和分泌炎性因子等作用的具体的路径；3.构建过表达的YAP和/或RASSF载体或siRNA干扰，验证了其在以上细胞及鼠模型细胞中的作用机制及其路径。本课题揭示了YAP在表皮KC异常增殖和炎症细胞分化中的关键作用机制，为寻找新的治疗靶点提供理论依据。