IL-17A在特发性肺纤维化患者肺成纤维细胞迁移和侵袭过程中的作用机制

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive and ultimately fatal disease with unknown aetiology and unclear pathogenesis. At present, there is no effective treatment except lung transplantation. Thus it is urgent to increase knowledge and explore effective treatment of this disease. This study bases on the hypothesis that IL-17A might play an essential role in the development of IPF through regulating lung fibroblasts adhesion, skeleton and/or MMPs pathway to mediate the cell migration and invasion. First, we intend to detect the difference of migration and invasion stimulated by IL-17A between lung fibroblasts from normal and IPF lung tissue. Second, we will detect changes of cell skeleton, adhesion and MMP molecules elicted by IL-17A in lung fibroblasts lines. Third, we want to investigate the molecule changes of IL-17A pathway in lung fibroblasts migration and invasion. Finally, we intend to detect the difference of lung fibroblasts migration and invasion between normal and IL-17-/- mice IPF model induced by bleomycin. This study will further clarify the mechanism of IL-17A in IPF and also encourage for development of a treatment against the IPF.

特发性肺纤维化（IPF）是一种病因不明、进行性发展的间质性肺疾病，目前除肺移植外无其他有效的治疗方法，亟需认识其关键机制，探索新的治疗方法，本项目基于"IL-17A可能通过调控细胞骨架重构、细胞间黏附和/或细胞外基质降解，来调节肺成纤维细胞迁移和侵袭能力，影响IPF进程。"的假设，以人肺成纤维细胞和小鼠作为主要研究模型，通过研究正常及IPF患者来源的肺成纤维细胞系和原代肺成纤维细胞IL-17A刺激前后细胞迁移侵袭能力变化；检测IL-17A刺激后细胞骨架调节蛋白、细胞黏附因子、MMPs表达及其激活情况；研究IL-17A下游通路对迁移侵袭相关分子的调节作用；最后在动物水平通过检测正常和IL-17敲除小鼠在博莱霉素刺激的IPF模型中，肺成纤维细胞的迁移和侵袭能力差异，阐明 IL-17A调控肺成纤维细胞迁移和侵袭能力的作用方式及机理。从而为IPF的诊断治疗提供有益线索和理论基础。