特发性肺纤维化（IPF）是一种病因不清预后极差的间质性肺病，其发病与免疫炎症损伤及过度修复有关。我们前期转录组测序发现，血管生成素样蛋白（ANGPTL2）及其受体LILRB2在IPF中异常高表达；免疫组化染色显示上皮细胞增高最为明显，且与预后相关。TGF-β1是重要的致纤维化因子,体外实验初步显示ANGPTL2/TGF-β1可互相调控。结合文献复习设想ANGPTL2在LILRB2的介导下与TGF-β1存在正反馈调控环路，在IPF中发挥促纤维化作用。拟进一步利用转基因小鼠及肺纤维化小鼠模型，探讨ANGPTL2/LILRB2在IPF发病中的作用及潜在的临床治疗价值；结合GEO数据库及生物信息学分析筛选参与该循环的关键因子；通过功能缺失与功能获得的实验策略，Luciferase、ChIP等实验方法进行验证。研究成果为ANGPTL2转化为治疗IPF的新靶标提供坚实的基础。

Idiopathic pulmonary fibrosis (IPF) is an unknown etiology of interstitial lung disease with dismal prognosis. Its development may be related to immune-mediated injury and excessively repairs. Our previous transcriptome-sequencing data found that the expression of angiopoietin like protein (ANGPTL2)as well as its legends LILRB2 were significantly increased in IPF patients, especially in the epithelial cells, which was confirmed by immunohistochemical studies. Its expression was also closely related with the prognosis of IPF. TGF-β1 is an important profibrosis factor. Our in vitro experiments showed that ANGPTL2/TGF-β1 can interact between each other. Based on literature review and our previous studies, we hypothesize ANGPTL2 regulates TGF- β1mediated by LILRB2 in a positive feedback loop and causes profibrotic effects on fibroblasts in the development of IPF. In order to examine this hypothesis, we will use transgenic mice and murine pulmonary fibrosis mouse model to validate the profibrotic function and potential clinical value of ANGPTL2/LILRB2; Bioinformatics analysis and text mining use GEO database will be employed to screen the key factors participated in this cycle; Strategies of loss of function and gain of function and Luciferase、ChIP、 Western blot、Qpcr et.al methods will be used to verify the key candidate factors. The achievement will provide reliable experimental and theoretical basis for ANGPTL2 converted to the new therapeutic targets for IPF.