TGFβ1作为放射性肺纤维化（RIPF）的关键调控因子，调节RIPF的具体机制仍不明。研究表明，TGFβ1下游的PAI-1在纤维化中具有重要作用。申请人前期在基因芯片、动物、人体水平均发现PAI-1与RIPF及其相关蛋白表达密切相关，利用RGD多肽抑制与TGFβ1存在交互作用的整合素αv可下调PAI-1的表达。因此申请者提出假设：PAI-1在TGFβ1诱导的RIPF中具有重要作用，可能是通过 “TGFβ1／整合素αv－PAI-1”通路导致RIPF的发生发展。本项目在细胞和动物水平上利用抑制剂及基因敲低、敲除技术，阐明PAI-1在TGFβ1诱导的放射性肺纤维化中的作用和机制，明确TGFβ1-整合素αv交互作用对PAI-1表达的调控，为以PAI-1为靶点开发全新的抗RIPF药物提供理论依据。

TGFβ1 is a key regulator in the progress of radiation induced pulmonary fibrosis (RIPF). However, the underlying mechanism remains unclear. Studies have shown that PAI-1, downstream of TGFβ1, plays an important role in pulmonary fibrosis. In our previous study, using cDNA microarray analysis to identify genes potentially involved in the development of RIPF, we showed that irradiated cell lines and murine lung tissues expressed elevated levels of PAI-1 relative to unirradiated group. In order to further clarify its role in RIPF, we did a series of experiments to verify the elevated expression of PAI-1 after radiation in vivo and in vitro. Furthermore, we found the expression of PAI-1 could be downregulated by the use of RGD peptides inhibiting the TGFβ1-integrin αv interaction. Therefore, the applicant put forward the hypothesis that PAI-1 plays an important role in TGFβ1-mediated RIPF, which may lead to the development of RIPF through the "TGFβ1 / integrin αv-PAI-1" pathway. Our project is aimed to figure out the effect of PAI-1 on TGFβ1-mediated RIPF, to disclose the effect of TGFβ1-integrin αv interaction on PAI-1 expression, and to develop a new targeting strategy for RIPF intervention.