YAP/TAZ介导角质形成细胞分化的机制研究

角质形成细胞参与黏膜局部炎症免疫-上皮信号转导的机制不明。口腔扁平苔藓（OLP）是常见的口腔黏膜炎性疾病，可作为研究免疫-上皮信号转导的良好模型。目前研究已发现，YAP/TAZ调控角质形成细胞功能对于上皮内稳态维持至关重要，然而在黏膜局部炎症微环境中，是否存在依赖于YAP/TAZ的角质形成细胞功能调控机制，有待阐明。申请人前期研究发现YAP/TAZ调控口腔黏膜角质形成细胞增殖分化，且在OLP角质形成细胞中表达降低，这可能是由于免疫细胞浸润导致细胞外基质（ECM）信号转导紊乱。本项目将以OLP为模型，研究以下三个方面内容：1.免疫细胞重塑ECM的主要途径；2.YAP/TAZ感受ECM信号转导的关键机制；3.YAP/TAZ调控角质形成细胞分化的核心网络。力争以此阐明角质形成细胞参与免疫-上皮信号转导的普遍规律，为黏膜炎性疾病的治疗方案研究提供科学依据。

The mechanism by which keratinocytes are involved in mucosal local inflammatory immune-epithelial signaling transduction is unknown. Oral lichen planus (OLP) is a common oral mucosal immune disease and can be used as a good model for studying immune-epithelial signaling transduction. Current studies have found that the regulation of keratinocyte function by YAP/TAZ is crucial for the maintenance of epithelial homeostasis. However, in the local mucosal inflammatory microenvironment, whether there is a YAP/TAZ-dependent regulation of keratinocyte function remains to be elucidated. The applicant's previous study found that decreased YAP/TAZ expression may be a key link in mediating OLP keratinocyte differentiation, which may be due to immune cell infiltration and remodeling of the extracellular matrix (ECM). This project will use OLP as a model to study the following three aspects: 1. The main pathway of immune cells to remodel ECM; 2. The key mechanism of YAP/TAZ sensing ECM signal transduction; 3. The core signaling network of YAP/TAZ regulates keratinocyte differentiation. We strive to elucidate the general mechanism of keratinocytes involved in immune-epithelial signal transduction and provide a scientific basis for the study of therapeutic regimens for mucosal immune diseases.