水通道蛋白3在玫瑰痤疮发病中的作用及机制研究

玫瑰痤疮是一种好发于中青年女性面部的慢性炎症性皮肤病，目前发病机制不明且无法治愈。固有免疫系统紊乱及血管功能失调是玫瑰痤疮发病的两个重要机制。已有报道显示水通道蛋白3（AQP3）能参与调控免疫炎症及血管功能，但其在玫瑰痤疮发病中的作用尚无报道。我们前期研究发现，玫瑰痤疮患者及小鼠模型组织中AQP3表达显著上升，且AQP3敲除鼠中，LL37诱导的玫瑰痤疮样表型被明显抑制，故推测AQP3可能参与玫瑰痤疮的发病。本研究中，我们将首先完善AQP3在玫瑰痤疮中的表达和定位研究；然后进行玫瑰痤疮患者及AQP3敲除鼠玫瑰痤疮模型皮损RNA测序，筛选差异表达基因，并进一步在小鼠体内及人角质形成细胞（KC）中验证其功能；最后采用共培养的方法体外验证在LL37刺激下，人KC中AQP3调控血管内皮细胞和免疫细胞功能的具体机制。本研究旨在揭示AQP3在玫瑰痤疮发病中的具体机制，为其临床治疗提供新的方向和依据。

Rosacea is well established as a chronic facial skin disease, which starts in affected women when they are between 30 and 50 years of age. The pathophysiology of rosacea remains uncertain. And currently, there is no known cure for this condition. Abnormalities in the innate immune system and neurovascular dysregulation have been considered to be primarily implicated in the pathophysiology of rosacea.Aquaporin-3 (AQP3) have been found to play roles in inflammation, immune response and blood vessel function. However, it remains unclear whether AQP3 is involved in rosacea. Our previous results showed that the expression level of AQP3 was significantly elevated in the rosacea patient and LL-37 treated mouse model. And rosacea-like phenotypes were inhibited in AQP3-/- mice treated with LL-37. Then we anticipated that AQP3 might function in the pathophysiology of rosacea. Here,we will first supplement the expression and location detection of rosacea. Then, using RNA-sequence, we will unearth differentially expressed genes in the tissue of the rosacea patient and mouse model. The functions of those genes will be furtherly identified in human and mouse keratinocytes. By applying co-culture system with LL-37 stimulation simultaneously, we will explore how AQP3 expressed in the human keratinocytes affects the functions of vascular endothelial cells(VECs) and immune cells. In summary,our findings will support AQP3 as a novel determinant in rosacea and hence a potential new therapeutic target.