Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy

作     者：Shuai Yuan Xudong Zhang Jiabing Zhan Rong Xie Jiahui Fan Beibei Dai Yanru Zhao Zhongwei Yin Qian Liu Dao Wen Wang Huaping Li Chen Chen 

作者机构：Division of CardiologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersWuhan 430030China Department of Forensic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2024年第67卷第6期

页      面：1155-1169页

核心收录：

学科分类：0710[理学-生物学] 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(U22A20266,82170273,81630010) the Fundamental Research Funds for the Central Universities(2019kfy XMBZ035,2021yjs CXCY090) Fundamental Research Funds of Wuhan Innovation Program(2022020801020451) 

主　　题：lncRNA fibroblast fibrosis dilated cardiomyopathy heart failure 

摘      要：CFIRL is a long noncoding RNA(lnc RNA),we previously identified as the most significantly upregulated lnc RNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function of CFIRL and its role in ***-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing *** knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction(TAC)-induced cardiac dysfunction and fibrosis in *** of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to *** knockdown attenuated these ***,RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1,a newly identified noncanonical transcriptional factor,to activate ***-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy,which can be prevented by CFIRL *** findings uncover the critical role of CFIRL,a fibroblast-associated lnc RNA,in heart failure by facilitating crosstalk between fibroblasts and *** knockdown might be a potent strategy to prevent cardiac remodeling in heart failure,particularly in DCM.