放射可引起放射性肺纤维化，成纤维细胞是肺纤维化的关键效应细胞，它的一个重要来源是肺泡上皮细胞发生的上皮间质转化（Epithelial mesenchymal transition, EMT），但放射损伤促进肺泡上皮细胞EMT机制不明。我们前期实验室提示DNA放射损伤关键调节分子DNA-PKcs在上述过程中可能发挥重要作用。本研究旨在探讨DNA-PKcs在放射诱导的肺泡上皮细胞 EMT发生中的作用及分子机制, 重点研究是否存在DNA 损伤启动的DNA-PKcs介导EMT的特殊信号通路，以及DNA-PKcs对经典TGF-β/Smad信号通路和非Smad信号通路的影响及调节机制；并筛选2-3个与放射诱导肺泡细胞EMT的密切相关分子，进行放射线诱导靶向基因治疗干预放射性肺纤维化的实验研究。本项目将更加深入地揭示放射所致的EMT发生的分子机制，为放射性肺纤维化的防治提供新的潜在靶点和重要理论依据。

Radiation causes radiation-induced pulmonary fibrosis. Fibroblast, as the key cells in pulmonary fibrosis, secretes the collagen with excessive deposition, which is the major contributor of pulmonary fibrosis. One of important sources of fibroblasts is alveolar epithelial mesenchymal transitions (EMT). The mechanism of EMT, especially radiation-induced EMT is still largely unclear. Our previous research revealed that DNA-PKcs, the important player in multiple points through the whole pathways of DNA damage signaling, repair and cellular responses, might play a very important role in the process of EMT. The study is intended to discuss the roles and the mechanism of DNA-PKcs in radiation-induced alveolar EMT，and the possible signal transduction pathway it could be involved. Further more，the 2-3 candidate proteins would be chosen for in vivo study on the effect of targeted gene therapy to prevent RIPF. The frontier theory and knowledge achieved in this project will provide valuable guidance for the development of innovative measures to protect and cure the radiation pulmonary fibrosis.