TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

作     者：Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang Lu Linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei Luo Hao Lu Zilun Wei Jian Wu Peng Yu Li Shen Xiaochun Zhang Aijun Sun Junbo Ge Shuai Song;Xiaokai Zhang;Zihang Huang;Yongchao Zhao;Shuyang Lu;Linqi Zeng;Fengze Cai;Tongyao Wang;Zhiqiang Pei;Xinyu Weng;Wei Luo;Hao Lu;Zilun Wei;Jian Wu;Peng Yu;Li Shen;Xiaochun Zhang;Aijun Sun;Junbo Ge

作者机构：Department of CardiologyZhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key Laboratory of CardiologyZhongshan HospitalFudan UniversityShanghaiChina Key Laboratory of Viral Heart DiseasesNational Health CommissionShanghaiChina Key Laboratory of Viral Heart DiseasesChinese Academy of Medical SciencesShanghaiChina National Clinical Research Center for Interventional MedicineShanghaiChina Department of cardiac surgeryZhongshan HospitalFudan UniversityShanghaiChina Institutes of Biomedical SciencesFudan UniversityShanghaiChina Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2024年第9卷第3期

页      面：1209-1220页

核心收录：

学科分类：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 China National Funds for Young Scientists(grant number 82000309 to Shuai Song,82200290 to Yongchao Zhao) the Shanghai Sailing Program(grant number 20YF1429600 to Shuai Song),Basic Science Center Project(grant number T2288101 to Junbo Ge) the National Natural Science Foundation(grant number 82130010 to Aijun Sun) the Shanghai Clinical Research Center for Interventional Medicine(grant number 19MC1910300 to Junbo Ge) Fuqing Scholar of Fudan University,Shanghai Medical School(grant number FQXZ202204B to Zihang Huang) 

主　　题：TEAD1 expression Wnt4 

摘      要：Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure *** TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 ***1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 ***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.