SIRT7在银屑病发病机制中的作用

SIRT7 is an important mediator of acetylation modulation in vivo, although it has never been found in the pathogenesis of psoriasis. We first found the elevated expression of SIRT7 in the eruption of psoriasis, in the epidermal specific SIRT7 transgenic mice has been constructed firstly by ourselves the mice has psoriasis-like phenotype. To elucidate the detail mechanism of SIRT7, mass spectral, acetylation analysis, GST-Pull down, Co-expression experiments, CHIP, luciferase reporter essay were used to find the target of SIRT7. The results indicate SIRT7 may modulate the immunity of skin through affect the acetylation state and the expression level of IRF-2. SIRT7 and IRF-2 locate in the psoriasis suspected locus PSOR2 and PSOR3 respectively, we use SNP seq and EMSA to analysis the SNP and DNA methylation variation, the primary data indicate the genetic polymorphism may affect the expression level of SIRT7 in the patients who have psoriasis. The project try to elucidate the effect of SIRT7 in the pathogenesis of psoriasis from four level: the genetic, transcription modulation, animal model and people to find the new pathogenesis and the new treatment target of psoriasis.

SIRT7为体内乙酰化调节的重要介质，其在银屑病中作用未见报道。我们首次发现银屑病皮损中存在SIRT7的高表达，同时首次构建表皮特异性SIRT7转基因小鼠，小鼠出现类银屑病样表型。为进一步解释SIRT7具体作用机制，我们应用质谱、乙酰化分析、GST-Pull down、共表达实验、染色质免疫共沉淀、荧光素酶报告实验等方法试图寻找SIRT7的作用靶点，前期结果提示SIRT7可能通过影响IRF-2的乙酰化水平及表达水平实现其皮肤炎症调节效应。SIRT7和IRF2分别位于银屑病致病区域PSOR2和PSOR3区，我们应用SNP seq、EMSA等方法，分析人群中SIRT7的单核苷酸突变及甲基化变异，提示银屑病人群中存在影响SIRT7表达的遗传变异。本课题试图从遗传学、转录表达调控、模式动物及人群四个层面系统研究SIRT7在银屑病发病机制中的作用，为进一步了解银屑病发病机制及治疗新靶点的寻找奠定基础

SIRT7为体内乙酰化调节的重要介质，其在银屑病中作用未见报道。我们首次发现银屑病.皮损中存在SIRT7的高表达，同时首次构建表皮特异性SIRT7转基因小鼠，小鼠出现类银屑病样.表型。为进一步解释SIRT7具体作用机制，我们应用质谱、乙酰化分析、GST-Pull down、共表.达实验、染色质免疫共沉淀、荧光素酶报告实验等方法试图寻找SIRT7的作用靶点，前期结果.提示SIRT7可能通过影响IRF-2的乙酰化水平及转录活性实现其皮肤炎症调节效应。SIRT7和IRF.2分别位于银屑病致病区域PSOR2和PSOR3区，我们应用SNPshot、荧光素酶报告实验等方法，分.析人群中SIRT7的单核苷酸突变，提示银屑病人群中存在影响SIRT7表达的遗传变异。本课题试.图从遗传学、转录表达调控、模式动物及人群四个层面系统研究SIRT7在银屑病发病机制中的.作用，为进一步了解银屑病发病机制及新靶点的寻找奠定基础。