LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation

作     者：Jian Sun Tongzhu Jin Zhihui Niu Jiayu Guo Yingying Guo Ruoxuan Yang Qianqian Wang Huiying Gao Yuhan Zhang Tianyu Li Wenxin He Zhixin Li Wenchao Ma Wei Su Liangliang Li Xingxing Fan Hongli Shan Haihai Liang Jian Sun;Tongzhu Jin;Zhihui Niu;Jiayu Guo;Yingying Guo;Ruoxuan Yang;Qianqian Wang;Huiying Gao;Yuhan Zhang;Tianyu Li;Wenxin He;Zhixin Li;Wenchao Ma;Wei Su;Liangliang Li;Xingxing Fan;Hongli Shan;Haihai Liang

作者机构：Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Northern Translational Medicine Research and Cooperation CenterHeilongjiang Academy of Medical SciencesHarbin Medical UniversityHarbin 150081China Department of Thoracic SurgeryShanghai Pulmonary HospitalTongji UniversityShanghai 200433China State Key Laboratory of Quality Research in Chinese Medicine/Macao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyMacao(SAR)China Research Unit of Noninfectious Chronic Diseases in Frigid Zone(2019RU070)Chinese Academy of Medical SciencesHarbin 150081China Zhuhai People's HospitalGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and TreatmentZhuhai Hospital Affiliated with Jinan UniversityJinan UniversityZhuhai 519000China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第9期

页      面：3602-3617页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (32171127 and 91949109) the HMU Marshal Initiative Funding (HMUMIF-21023, China) the Major Scientific Fund Project of Heilongjiang Province (ZD2019H001, China) the CAMS Innovation Fund for Medical Sciences (CIFMS, 2019-I2M5-078, China) the Guangdong Province Basic and Applied Basic Research Fund (2021A1515111049, China) Postgraduate Research and Practice Innovation Program of HMU (YJSCX202015HYD, China) 

主　　题：Idiopathic pulmonary fibrosis LncRNA DACH1 SRSF1 CTNNB1 Fibroblast Myofibroblast Extracellular matrix Proliferation 

摘      要：Idiopathic pulmonary fibrosis(IPF)is a progressive disease with unknown etiology and limited therapeutic *** of fibroblasts is a prominent feature of pulmonary *** we report that lncRNA DACH1(dachshund homolog 1)is downregulated in the lungs of IPF patients and in an experimental mouse model of lung ***1 knockout mice develop spontaneous pulmonary fibrosis,whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation,collagen deposition and differentiation of mouse lung ***,forced expression of LncDACH1 not only prevented bleomycin(BLM)-induced lung fibrosis,but also reversed established lung fibrosis in a BLM ***,LncDACH1 binding to the serine/arginine-rich splicing factor 1(SRSF1)protein decreases its activity and inhibits the accumulation of *** expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung ***,loss of LncDACH1 promoted proliferation,differentiation,and extracellular matrix(ECM)deposition in mouse lung fibroblasts,whereas such effects were abolished by silencing of *** addition,a conserved fragment of LncDACH1 alleviated hyperproliferation,ECM deposition and differentiation of MRC-5 cells driven by TGF-β***,LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation,suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.