尘肺是我国的头号职业病，矽肺又占近一半，目前缺乏有效防治方法。骨髓间充质干细胞（BMSC）对多种疾病的防治作用已展示良好的应用前景。本课题组以往的研究表明BMSC能减轻实验性矽肺小鼠肺部病变。最近我们发现，在该模型中BMSC能抑制肺泡巨噬细胞（MΦ）NALP3炎性小体通路，转录组测序结果显示BMSC中的TSG-6基因转录水平上调。本项目拟利用小鼠矽肺模型及体外细胞学实验，研究①BMSC分泌的TSG-6在BMSC减轻实验性矽肺病变中的作用；②BMSC分泌的TSG-6与肺泡MΦ表面CD44分子的作用及调控NALP3炎性小体的模式。通过研究TSG-6、CD44及NALP3炎性小体的相互作用，揭示BMSC减轻实验性矽肺病变的分子机制，阐明BMSC发挥保护效应的关键分子及信号通路。该研究将为开展BMSC治疗矽肺的临床研究提供临床前研究数据，并为靶向调控BMSC治疗矽肺提供新的策略和靶点。

Pneumoconiosis constituted half of silicosis is the most extensive occupational disease in China, which still has not effective methods for prevention and treatment. Bone mesenchymal stem cells has wide application prospects in disease treatment. Our group recently demonstrated that BMSC attenuated silica-induced lung injuries. Recently, we found BMSC could inhibit NALP3 inflammasome in macrophage. Using the RNA-Seq, we found the TSG-6 mRNA of BMSC increased. Thus, using experiments in vivo and in vitro, this proposal aims to: ① Determine the function of TSG-6 in BMSC which attenuates silica-induced lung injuries. ②Explore the interaction between TSG-6 and CD44 on macrophage and the regulatory function of NALP3 inflammasome. The project will define the molecular mechanism of BMSC which attenuates silica-induced lung injuries and the key molecular and pathway through studying the interaction between TSG-6, CD44 and NALP3 inflammasome. In addition, this study can provide pre-clinical data for the clinical trial and develop novel strategies for silicosis therapies.