肺纤维化是严重危害人类健康的一种疾病，目前尚无有效治疗方法。研究表明，肺纤维化的发生与上皮间质转化（EMT）有密切关系，EMT的发生则主要受FGFR2选择性剪切的调控，而上皮剪切调节蛋白（ESRP）又是选择性剪切发生的决定因素。同时鉴于肺纤维化发生时TGF-beta与bFGF有明显增高，两者又是EMT的主要诱导因子，因此我们推测，肺纤维化发生时TGF-beta与bFGF增高，激活Smad与非Smad信号通路，导致ESRP表达受抑，FGFR2上皮型选择性剪切减少，EMT发生，肺纤维化形成。为证明该假设，本项目拟采用定量PCR、WesternBlot、免疫组织化学、RNAi等技术，通过体内外实验，确定肺纤维化与EMT发生时ESRP表达的变化规律，明确ESRP对肺纤维化形成的作用与意义，阐明肺纤维化过程中ESRP改变的分子机制，探讨ESRP调控对肺纤维化的影响，从而为肺纤维化的防治提供理论依据。

Lung fibrosis is an important disease, and without any effective therapy methods. Present researches shows that the occurrence of lung fibrosis is closely associated with epitahlial mesenchymal transition (EMT), and the EMT is greatly depended on alternative slplicing changes of fibroblast growth factor receptor 2. Then, the Epithelial Splicing Regulatory Protein (ESRP) is found to decide the alternative splicing. Meanwhile, TGF-beta and bFGF which are predominant inducible factors of EMT are incresed in lung fibrosis. So, we suggested that increased TGF-beta and bFGF will activate Smad and non-Smad signal pathway, and restrain the expression of ESRP which will lead to FGFR2 IIIb choice. Then EMT is emerging and developed into lung fibrosis. To validate this suggestion, we try to identify the changes of ESRP expression during EMT and lung fibrosis, to understand the effect and significance of ESRP on lung fibrosis, to clarify the molecular mechanism of ESRP changes, to explore the effect of ESRP regulatory on the fibrosis. This study will support the prevent and treatment of lung fibrosis.