肺纤维化是各种原因所致慢性肺部疾病的创伤愈合反应，表现为肺泡结构紊乱和结缔组织过度沉积，导致不可逆的呼吸功能衰竭，目前尚无有效治疗药物。随着我国老龄化社会的来临和雾霾的频繁来袭，研制抗肺纤维化的药物迫在眉睫。该项目拟在前期筛选的海洋生物活性成分虾青素及其长链非编码RNA-lncITPF的基础上，以肺纤维化动物及细胞模型为筛选系统，结合肺纤维化临床患者和正常健康人标本，应用RNA pull down、Chirp、chip-seq等技术研究虾青素是否通过影响甲基化/组蛋白修饰以及转录因子结合调控lncITPF转录，深入研究虾青素作用下lncITPF通过结合核内不均一核糖核蛋白L(hnRNP L)调控生物信息的传递与表达的机制，为开发研制有效防治肺纤维化的海洋生物药提供实验依据。同时以lncITPF为药物的作用靶点，设计针对lncITPF的基因干扰药物，为肺纤维化的基因靶向治疗奠定基础。

Pulmonary fibrosis is the reaction caused by different kinds of chronic lung disease, wound healing, mainly for excessive deposition of connective tissue and alveolar structure disorder, leading to respiratory failure is not reversible. Now there is no effective drug treatment. Therefore, exploring the underlying molecular mechanisms, developing predisposition or diagnostic biomarkers, new therapeutic drugs has important clinical value. In our previous study, we found astaxanthin, obtained from shrimp and crab, could relieve the symptoms and halt the progression of pulmonary fibrosis. Meanwhile, the long non coding RNA-lncITPF, named by our group, was regulated by astaxanthin. In this project, we employ TALENs and CRISPR/Cas9 technology to directly target the lncITPF gene in alveolar epithelial cell and fibroblasts. Then using RNA pull down, Chirp, chip-seq, rescue experiments, we explored the role of astaxanthin on the lncITPF transcriptional regulation by affecting methylation and histone modification in promoter regions. And exploring whether lncITPF regulate its targeted genes by interacting with hnRNP L under astaxanthin treatment. Meanwhile, using IPF patients samples, we aimed to explored whether lncITPF could be a early diagnostic biomarker for IPF disease. This research provided scientific experimental data for developing potential biomarker, therapeutic target and marine biological drugs for lung fibrosis.