GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases
作者机构：Department of CardiologyZhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032China Department of CardiologyZhongshan HospitalFudan UniversityShanghai 200032China Department of Medical ExaminationShanghai Xuhui District Central HospitalShanghai 200031China Department of Cardiology and Institute of Clinical MedicineRenmin HospitalHubei University of MedicineShiyan 442000China Clinical Data CenterChildren’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of MolecularCelland Cancer BiologyUniversity of Massachusetts Chan Medical SchoolWorcesterMA 01605USA Bio-X InstituteKey Laboratory for The Genetics of Developmental and Neuropsychiatric DisordersShanghai Jiao Tong UniversityShanghai 200030China Department of CardiologyHeart Center of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Department of CardiologySir Run Run Shaw Hospitalaffiliated with Zhejiang University School of MedicineHangzhou 310020China Department of CardiologyThe Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of CardiologyShanghai Xuhui District Central HospitalShanghai 200031China Department of CardiologyShanghai Eighth People’s HospitalShanghai 200235China Department of Chemistry and Institutes of Biomedical SciencesFudan UniversityShanghai 200032China State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China School of Life Science and TechnologyShanghai Tech University100 Haike RoadShanghai 201210China Key Laboratory of Systems Health Science of Zhejiang ProvinceSchool of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Pulmonary and Critical Care MedicineZhongshan HospitalShanghai Medical CollegeFudan UniversityShanghai 200032China State Key Laboratory of CardiologyZhongshan HospitalFudan UniversityShanghai 200032China National Clinical Research Center for Interventional MedicineShanghai 200032China Shanghai Clinical Research Center for Interventional MedicineShanghai 200032China Key Laboratory of Viral Heart DiseasesNational Health CommissionShanghai 200032China Key Laboratory of Viral Heart DiseasesChinese Academy of Medical SciencesShanghai 200032China
出 版 物：《The Innovation》 (创新（英文）)
年 卷 期：2024年第5卷第2期
页 面：27-41页
核心收录：
基 金：This work was supported by the National Natural Science Foundation of China(82170334 and 81870182)。
主 题：ischemic activation GTF
摘 要：Partial endothelial-to-mesenchymal transition(EndMT)is an intermediate phenotype observed in endothelial cells(ECs)undergoing a transition toward a mesenchymal state to support neovascularization during(patho)physiological angiogenesis.Here,we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4(GTF2H4)as a positive regulator of this process.In addition,we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3(ERCC3)to co-regulate partial EndMT.Furthermore,by using phosphorylation proteomics and site-directed mutagenesis,we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3(NCOA3)at serine 1330,which promoted the interaction between NCOA3 and p65,resulting in the transcriptional activation of NF-κB and the NF-kB/Snail signaling axis during partial EndMT.In vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic injury.Collectively,our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.
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