SIK2在放射性肺纤维化中的作用及机制研究

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（EMT），但其机制尤其是放射损伤促进肺泡上皮细胞的EMT机制不明。我们前期实验结果提示SIK2在上述过程中可能发挥重要作用。本研究旨明确SIK2在辐射诱导的肺泡EMT发生中的作用及分子机制, 探讨SIK2与PIK3R2相互作用对PI3K/AKT信号通路的影响以及辐射依赖的以SIK2为核心的特异EMT信号通路及其调节机制，明确SIK2在RIPF发生中的作用及作为RIPF潜在治疗靶点的可能性。并筛选2-3条以SIK2为核心的参与辐射诱导肺泡细胞EMT的特异分子，进行放射线诱导靶向基因治疗干预放射性肺纤维化的体内实验研究。本项目将更加深入地揭示电离辐射所致的EMT发生的分子机制，将为放射性肺纤维化的防护和治疗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 effector 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 SIK2 might play a very important role in the process of EMT. The study is intended to discuss the roles and the mechanism of SIK2 in radiation-induced alveolar EMT，focusing on the function of interaction between SIK2 and PIK3R2 on PI3K/AKT signal transduction pathway, and radiation-dependent signal 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.