Sprouty1通过调控晚期角质化包膜蛋白影响银屑病表皮屏障的机制研究

银屑病是一种免疫介导的复发性炎症性疾病，主要累及皮肤，也常合并关节、心血管等病变。目前尚无法彻底治愈银屑病。皮肤屏障受损和免疫调节失衡被认为是银屑病发病的重要因素。我们前期实验发现Sprouty1可以影响人角质形成细胞的增殖、分化和凋亡，且从蛋白水平证实了Sprouty1在银屑病表皮中低表达；表皮过表达Sprouty1减轻了小鼠咪喹莫特诱导的银屑病样皮肤炎症，下调表皮抗菌肽的表达；表皮条件敲除Sprouty1的小鼠自发出现表皮增厚、红斑、鳞屑等银屑病样皮肤炎症，以及关节肿胀变形。综上已有数据，表明Sprouty1在银屑病发病中发挥重要作用，影响表皮角质化包膜的形成，进而调节表皮物理屏障和免疫屏障的功能。但是，Sprouty1调控表皮屏障功能的具体机制尚未阐明。因此，本项目旨在进一步探讨Sprouty1通过调控晚期角质化包膜蛋白影响皮肤屏障功能，及在银屑病发生发展及转归中的作用机制。

Psoriasis is an immune-mediated recurrent inflammatory disease, that mainly affects the skin, but also often involves joints and cardiovascular system. There is no cure for psoriasis yet. Impaired skin barrier and imbalance of immune regulation are considered as important factors in the pathogenesis of psoriasis. Our previous data found that Sprouty1 can inhibit the human keratinocytes proliferation, promote keratinocytes differentiation and regulate their apoptosis. We also confirmed that the expression of Sprouty1 decreased in psoriasis epidermis at protein level. In addition, epidermis-specific overexpression of Sprouty1 alleviated imiquimod-induced psoriasis-like skin inflammation in mice model, and down-regulated epidermal antimicrobial peptides. Consistently, epidermis-specific conditional knock out Sprouty1 mice spontaneously develop psoriasis-like skin inflammation, characterized epidermal thickening, erythema, and scales, as well as joints swelling and deformation. In summary, our data indicated Sprouty1 plays an important role in the pathogenesis of psoriasis, affecting epidermal cornified envelope formation, and regulating epidermal physical barrier and immune barrier. However, the specific mechanism of Sprouty1 regulating epidermal barrier function has not been elucidated. Therefore, this study aims to deepen the mechanism that Sprouty1 affects the skin barrier by regulating late cornified envelopes, and further explore the role of Sprouty1 in the initiation, development and outcome of psoriasis.