紧密连接是介导物质经上皮细胞旁细胞途径转运的蛋白复合体，但对其在下颌下腺中的作用了解甚少。本项目将与韩国首尔国立大学的Park教授密切合作，通过举办联合学术年会、实验技术交流会、联合发表论文等多种方式进行学术交流，以肿瘤坏死因子α（TNF-α）等细胞因子诱导的下颌下腺炎症反应为主线，紧密连接蛋白为重点，采用免疫印迹、免疫荧光、基因敲低或过表达等方法证实紧密连接蛋白在下颌下腺紧密连接中的作用；在TNF-α诱导的大鼠下颌下腺炎和SMG-C6细胞上观察紧密连接蛋白表达、分布和功能的变化，在器官、细胞和分子水平证实紧密连接蛋白是TNF-α特异性调控的紧密连接靶分子；以ERK1/2和NF-κB通路为中心，探讨TNF-α调控紧密连接蛋白表达和功能的信号转导途径。本研究将丰富紧密连接介导下颌下腺分泌的理论，揭示紧密连接蛋白在下颌下腺的生理功能，明确TNF-α调控紧密连接蛋白的分子机制，并为探讨以紧密连接为靶点防治下颌下腺炎症性疾病提供新的思路。

Tight junction is a protein complex for materials transport through paracellular route in epithelial cells, however, its exact role in submandibular gland is still unclear. The project will cooperate closely with professor Park at Seoul National University, including organizing the joint annual conference, experimental and technological exchanges, and publishing articles together. Our present study will focus on the effects of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) on the tight junction proteins in submandibular gland. By using immunoblotting, immunofluorescence, gene knockdown and overexpression, we will explore the roles of tight junction proteins in submandibular tight junction function. On the TNF-α-induced rat submandibular inflammation and cellular model, we will detect the changes of the expression, distribution and function of tight junction proteins, aiming to determine the potential targets for TNF-α from both organic and cellular levels. We will further investigate the signaling pathway connecting TNF-α with tight junction proteins, especially focusing on ERK1/2 and NF-κB signaling pathways. This study will identify the physiological and pathophysiological significance of tight junction proteins in submandibular gland, explore the molecular mechanism involved in the TNF-α-regulated tight junction proteins, and further provide a novel insight into a future therapeutic target for inflammatory diseases of submandibular gland.