血管生成素的基因多态性与银屑病的关系及其作用机制的研究

Psoriasis is a common chronic inflammatory skin disease. Genetic and environment factors are generally thought to be involved in psoriasis. Treatment for psoriasis are currently insufficency.Angiogenesis is the characteristic of psoriasis pathology. Our previous studies showed angiopoietin and caspase 3,5 were highly expressed in psoriasis, and several Ang2 polymorphisms are related with psoriasis.Moreover, the expression pattern of Ang2 and Caspase 3,5 are similar,suggesting the interaction of them. This proposal will detect the function of Ang from two aspects: 1. At the genetic level: study on the correlation between Ang and psoriasis through detecting the single nucleotide polymorphism (SNP)of Ang;Detect serum levels of caspase 3,5 and cytokines in psoriasis patients with different Ang genotype.2.At cell level:check the effect of angiopoietin on caspase 3,5 as well as keratinocyte proliferation and infiltration.This proposal may be extremely valuable to define a novel agent for the treatment of psoriasis.

银屑病是一种常见的慢性炎症性皮肤病，发病机制仍不清楚，目前临床上缺乏特异、有效的治疗靶点和干预手段。真皮乳头微血管形成是银屑病重要的病理特征之一，我们的前期工作发现，促血管形成因子血管生成素(angiopoietin，Ang)的基因多态性及高表达与银屑病的发病密切相关，并且在银屑病皮损中，Ang2与半胱氨酸蛋白酶3、5的分布基本一致，提示Ang与半胱氨酸蛋白酶可能存在作用。本项目拟在前期研究发现基础上，在两方面探讨Ang在银屑病中的作用：1，在遗传学水平上：通过大样本对银屑病中Ang1、2基因中SNP位点的检测，明确Ang基因多态性与银屑病发病的关系；检测Ang 1,2不同基因型患者血中半胱氨酸蛋白酶3,5与炎性因子的表达。2，在细胞水平上：探讨Ang1、2对半胱氨酸蛋白酶3、5的作用机制及其对表皮增殖及炎症细胞浸润的影响，为寻找和开发新的靶向治疗银屑病药物奠定理论基础。

银屑病是一种常见的慢性炎症性皮肤病，其发病机制仍不清楚，普遍认为是遗传因素与环境因素相互作用的结果。目前临床上缺乏特异、有效的治疗靶点和干预手段。研究显示半胱氨酸蛋白酶（Caspase）家族与银屑病的发病密切相关。本项目从Caspases可能在银屑病的发生和发展中起重要作用入手，拟在两方面探讨Caspases在银屑病中的作用：1：在遗传学水平上：通过对银屑病特异性Caspases基因中SNP位点的检测，探讨Caspases基因多态性与银屑病发病的关系2：在细胞水平上：探讨Caspases在银屑病血管增生中的作用机制，为寻找和开发新的靶向治疗银屑病药物奠定理论基础。