项目名称： 骨形成蛋白6在舍格伦综合征发病作用的研究

项目编号： No.81470759

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王昊

作者单位： 首都医科大学

项目金额： 73万元

中文摘要： 舍格伦综合征 (Sj?gren's syndrome, SS) 是一种主要累及外分泌腺的慢性、系统性的自身免疫性疾病。本课题组前期研究发现SS病人及动物模型骨髓间充质干细胞（mesenchymal stem cells, MSCs）多向分化、自我复制及免疫调节功能严重受损，可能是SS发病机制之一，并发现SS骨髓MSCs骨形成蛋白6 (BMP6)特异增高。但唾液腺是否也存在MSCs？BMP6升高在SS发病中起何作用均不清楚。本研究将通过探讨唾液腺是否存在MSCs，观察唾液腺MSCs生物学及免疫学特性，正常唾液腺MSCs中BMP6过表达后对其免疫调节能力及对上皮细胞有何影响，并通过将体内BMP6阻断观察预防或减缓SS疾病进展的效果，来研究BMP6在SS发病中的作用，有望进一步深入了解SS发病机理，为SS的预防、早期诊断及治疗提供新方法，同时为其他自身免疫病的机理及临床研究提供新思路。

中文关键词： 舍格伦综合征；涎腺疾病；间充质干细胞；骨形成蛋白6

英文摘要： Sj?gren syndrome (SS) is a chronic, systemic autoimmune disorder characterized by inflammation of exocrine glands and functional impairment of the salivary and lacrimal glands characterized by dry mouth and dry eyes. Previously, we examined the properties of bone marrow mesenchymal stem cells (MSCs) in patients and SS-like mice, and found their immunoregulatory functions were defective during SS pathogenesis. However, it is still not clear how the damaged MSCs in bone marrow can cause the insufficiency of salivary gland in SS. Lately, a study reported a significant high level of bone morphogenetic protein 6 (BMP6) in labial gland of SS patients. And in our previous study we also found the over expression of BMP6 in bone marrow MSCs both in SS patients and mice. Base on previous studies, this project want to prove the existence of MSCs derived from salivary gland (SGMSCs), and whether these SGMSCs were defective during SS pathogenesis; whether over expression of BMP6 can affect the immunologic regulatory functions in SGMSCs and the secrete functions of salivary gland. Moreover, we will make an in vivo study to block the BMP6 in SS animal model and observe the dynamic change of SS symptoms in those animal. This work will provide a further understanding of the pathogenesis of SS, and will shed light on diagnosis and treatment for SS.

英文关键词： Sjogren's syndrom;salivary gland disease;mesenchymal stem cells;bone morphogenetic protein 6