银屑病是一种慢性炎症性皮肤病，角质形成细胞（KC）炎症反应参与其发病机制，但具体机制尚不清楚。申请人前期研究发现，Yes相关蛋白（YAP）在银屑病皮损中高表达，并通过调控KC的增殖、凋亡等参与发病过程，RAS相关结构域家族1A（RASSF1A）在银屑病皮损中表达降低，作为YAP上游负性调控因子，推测其可能在银屑病发病机制中发挥重要作用。本课题拟：①检测RASSF1A在银屑病中的甲基化情况，并分析其与YAP表达的相关性；②体外细胞实验证实RASSF1A可通过调控Hippo-YAP信号通路激酶相关因子磷酸化，从而影响银屑病炎症微环境下KC增殖、凋亡等生物学过程；③用银屑病小鼠模型验证上述结论，并设计逆转RASSF1A甲基化水平技术，来延缓银屑病皮损的进展。本课题对于揭示RASSF1A-Hippo-YAP信号通路在银屑病表皮异常增殖中的作用机制有重要意义，有望为寻找银屑病治疗的新靶点提提供思路。

Psoriasis is a chronic inflammatory skin disease. The keratinocyte-mediated inflammation is pivotal in the pathogenesis of psoriasis, although its detailed mechanism remains unclear. Our previous studies showed that the expression of Yes-associated protein (YAP) is upregulated in psoriatic skin, and YAP participates in the regulation of the proliferation and apoptosis of keratinocytes. RAS-association domain family 1A (RASSF1A), a negative upstream regulator of YAP, is down-regulated in psoriatic skin, so it is speculated to be important in the pathogenesis of psoriasis. Therefore, the purposes of this study are: ①To elucidate the methylation of RASSF1A gene as well as the its correlation with the expression of YAP in psoriatic skin; ②To reveal the RASSF1A regulation of phosphorylation of the core parts of kinase cascade in Hippo-YAP signaling pathway in vitro, which may affect the key biological processes including proliferation and apoptosis of keratinocytes under psoriatic microenvironment; ③To verify the hypothesis by using the imiquimod-induced psoriatic murine model, and also to design certain approaches to reverse the methylation of RASSF1A, which may delay the progression of skin lesions in this model. The results from this study will contribute to the elucidation of the mechanism of RASSF1A-Hippo-YAP pathway underlying the epidermal abnormal proliferation of psoriasis, and provide novel therapeutic target in the treatment of psoriasis.