宁夏为我国主要煤炭和建材基地，矽肺占该地区职业病的58.9%，严重影响劳动者的生活质量和生命，是该地区许多家庭致贫和返贫的主要原因。因此对矽肺发生、发展和防治机制的研究，有着重要的科学与现实意义。矽肺是一种特殊类型的肺纤维化疾病，研究表明Wnt/β-catenin参与肺脏的损伤修复和肺脏纤维化的病理发生，但其调控肺泡微环境炎性信号在矽肺病理发生的机制不明。本项目将在构建人肺泡微环境体外模型的基础上，通过(1) 探讨肺泡上皮细胞Wnt/β-catenin调控二氧化硅诱导肺泡巨噬细胞炎性反应的作用机制；(2) 分析肺泡上皮细胞Wnt/β-catenin调控肺泡微环境炎性信号对肺脏成纤维细胞间质化特性的影响；(3)利用MyD88缺陷小鼠，探讨小鼠矽肺模型肺泡微环境 Wnt/β-catenin和TLR交互作用在二氧化硅诱导矽肺的病理发生机制，为深入研究矽肺的致病机制提供新的思路和靶点。

Ningxia is an important industry basis of coal and constructive materials in China. Pneumoconiosis caused by dust is the main occupational disease that is as high as by 90.5% in this region, among them 58.9% are silicosis. Silicosis has caused a significantly negative impact on the quality of life and even the live of labors, which is the reason of causing and returning the poor for families with silicosis patients in Ningxia Hui Autonomous region. Therefore there is a scientific and actual significance in studying mechanisms in the development, progression and control of silicosis. It has been recognized that silicosis is a specific disease type of pulmonary fibrosis, and the Wnt/β-catenin signaling has been demonstrate to be involved in the injury repair of lung and the pathogenesis of pulmonary disease. However its role and underlying mechanism of Wnt/β-catenin signaling-regulated inflammary signaling of alveolar microenvironment in the pathogenesis of silicosis require a further investigation. This proposal thus about aims to explore the mechanism and regulatory role of Wnt/β-catenin signaling in alveolar microenvironment druing the pathogenesis of silicosis via an accomplishment of following three specific aims upon the establishment of in vitro alveolar microvironmental model: (1) in vitro study to demonstrate the impact of alveolar epithelia-derived Wnt/β-catenin signaling on silicon dioxide-induced inflammation in alveolar macrophages; (2) in vitro study to demonstrate the impact of interaction between alveolar epithelial Wnt/β-catenin and inflammatory signaling on the interstitial properties of pulmonary fibroblast in alveolar microenvironment; and (3) uncovering the potential mechanisms and pathogenic and immunoregulatory roles of interaction between epithelail Wnt/β-catenin and TLR signaling of macrophage in the pathogenesis of silicon dioxide-induced mouse silicosis using a MyD88-deficient mouse model. An accomplishment of this study will provide a novel insight for further studies of pathogenesis and targets for novel therapy of silicosis disease.