首页|Fibroblast-localized IncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy

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

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CFIRL is a long noncoding RNA(lncRNA),we previously identified as the most significantly upregulated lncRNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function of CFIRL and its role in DCM.Real-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 hearts.Global knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction(TAC)-induced cardiac dysfunction and fibrosis in vivo.Overexpression of CFIRL in vitro promoted fibroblast proliferation and aggravated an-giotensin Ⅱ-induced differentiation to myofibroblasts.CFIRL knockdown attenuated these effects.Mechanistically,RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1,a newly identified noncanonical transcriptional factor,to activate IL-6 transcription.IL-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy,which can be prevented by CFIRL knockdown.These findings uncover the critical role of CFIRL,a fibroblast-associated lncRNA,in heart failure by facilitating crosstalk between fibroblasts and cardiomyocytes.CFIRL knockdown might be a potent strategy to prevent cardiac remodeling in heart failure,particularly in DCM.

lncRNAfibroblastfibrosisdilated cardiomyopathyheart failure

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

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Division of Cardiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders,Wuhan 430030,China

Department of Forensic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds of Wuhan Innovation ProgramFundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities

U22A20266821702738163001020220208010204512019kfyXMBZ0352021yjsCXCY090

2024

10.1007/s11427-023-2452-2

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(6)
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