丝氨酸蛋白酶抑制剂B3/4在玫瑰痤疮中的表达、作用及机制研究

玫瑰痤疮是一种炎症性皮肤病，发病机制不明。文献表明丝氨酸蛋白酶抑制剂B3/4（SERPINB3/4）在多种炎性疾病中表达升高，但作用机制未知。我们前期发现玫瑰痤疮患者及小鼠皮损中SERPINB3/4表达升高，沉默小鼠Serpinb3a后玫瑰痤疮表型明显减轻，推测SERPINB3/4在玫瑰痤疮中发挥促炎作用。本研究中，我们将首先检测患者血清中SERPINB3/4的表达及与疾病严重程度相关性。而后调控人角质形成细胞中SERPINB3/4的表达，经LL37刺激后通过共培养检测其对玫瑰痤疮相关免疫细胞或血管内皮细胞功能的影响。再用沉默Serpinb3a的小鼠行玫瑰痤疮建模，取皮损行转录组测序，筛选介导SERPINB3/4作用的关键下游分子。最后，同时调控SERPINB3/4和关键分子的表达验证其功能及机制。本研究旨在探索SERPINB3/4在玫瑰痤疮中表达及作用机制，为玫瑰痤疮的治疗提供新的方向。

Rosacea is a common inflammatory disease the mechanism of which remains elusive. Previous publications established that SERPINB3/4 were over-expressed in various inflammatory diseases. Our preliminary results proved that the expression of SERPINB3/4 were markedly elevated in both rosacea patients and mouse model. Silencing of Serpinb3a significantly alleviated the rosacea-like phenotype in mouse, indicating that SERPINB3/4 might play an anti-inflammatory role in rosacea. In this study, we will first examine the expression of SERPINB3/4 in the serum of rosacea patients and its correlation with the severity of rosacea. Secondly, by regulating the expression of SERPINB3/4 in human keratinocytes, we will co-culture these keratinocytes with rosacea-related immune cells or endothelial cells to investigate the effect of SERPINB3/4 on the function of immune cells or endothelial cells after LL37 simulation. Thirdly, by establishing rosacea mouse model after silencing Serpinb3a, we will collect the lesions of mice and send them for transcriptome sequencing to screen out the key downstream effector molecules mediating the function of SERPINB3/4. Finally, by regulating the expression of SERPINB3/4 and downstream molecules simultaneously, we will further validate the function and mechanism of SERPINB3/4 and downstream molecules in rosacea. Our study is aimed to explore the expression, function and mechanism of SERPINB3/4 in rosacea, which might provide new possible directions for the treatment of rosacea in future.