GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases

doi:10.1016/j.xinn.2024.100565

	GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases
	Fang, Zheyan 1; Zhao, Gang 2; Zhao, Shuang 3; Yu, Xueting 1; Feng, Runyang 1; Zhang, You-en 4; Li, Haomin 5; Huang, Lei 6; Guo, Zhenyang 1; Zhang, Zhentao 1; Abdurahman, Mukaddas 1; Hong, Hangnan 1; Li, Peng 1; Wu, Bing 4; Zhu, Jinhang 7; Zhong, Xin 2; Huang, Dong 2; Lu, Hao 2; Zhao, Xin 2; Chen, Zhaoyang 8; Zhang, Wenbin 9; Guo, Junjie 10; Zheng, Hongchao 11; He, Yue 12; Qin, Shengying 7; Lu, Haojie 13; Zhao, Yun14,15,16 ; Wang, Xiangdong 17; Ge, Junbo 1,2,18,19,20,21,22; Li, Hua 1
	2024-03-04
发表期刊	INNOVATION (IF:33.2[JCR-2023],31.8[5-Year])
ISSN	2666-6758
EISSN	2666-6758
卷号	5 期号:2
发表状态	已发表
DOI	10.1016/j.xinn.2024.100565
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-κB/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. © 2024 The Author(s)
关键词	Amino acids Chemical activation Endothelial cells Molecular biology Transcription Angiogenesis Coactivators Complementation Endothelial-cells Excision repair Ischemic conditions Neo-vascularization Proteomics Site directed mutagenesis Target proteins
收录类别	EI
语种	英语
出版者	Cell Press
EI入藏号	20240815569520
EI主题词	Phosphorylation
EI分类号	461.9 Biology ; 802.2 Chemical Reactions ; 804 Chemical Products Generally ; 804.1 Organic Compounds
原始文献类型	Journal article (JA)
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/349975
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_赵允组
通讯作者	Li, Haomin; Ge, Junbo; Li, Hua
作者单位	1.Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai; 200032, China; 2.Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai; 200032, China; 3.Department of Medical Examination, Shanghai Xuhui District Central Hospital, Shanghai; 200031, China; 4.Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan; 442000, China; 5.Clinical Data Center, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou; 310052, China; 6.Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester; MA; 01605, United States; 7.Bio-X Institute, Key Laboratory for The Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai; 200030, China; 8.Department of Cardiology, Heart Center of Fujian Province, Fujian Medical University Union Hospital, Fuzhou; 350001, China; 9.Department of Cardiology, Sir Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine, Hangzhou; 310020, China; 10.Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao; 266003, China; 11.Department of Cardiology, Shanghai Xuhui District Central Hospital, Shanghai; 200031, China; 12.Department of Cardiology, Shanghai Eighth People's Hospital, Shanghai; 200235, China; 13.Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai; 200032, China; 14.State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai; 200031, China; 15.School of Life Science and Technology, Shanghai Tech University, 100 Haike Road, Shanghai; 201210, China; 16.Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou; 310024, China; 17.Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai; 200032, China; 18.State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai; 200032, China; 19.National Clinical Research Center for Interventional Medicine, Shanghai; 200032, China; 20.Shanghai Clinical Research Center for Interventional Medicine, Shanghai; 200032, China; 21.Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai; 200032, China; 22.Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai; 200032, China
推荐引用方式 GB/T 7714	Fang, Zheyan,Zhao, Gang,Zhao, Shuang,et al. GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases[J]. INNOVATION,2024,5(2).
APA	Fang, Zheyan.,Zhao, Gang.,Zhao, Shuang.,Yu, Xueting.,Feng, Runyang.,...&Li, Hua.(2024).GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases.INNOVATION,5(2).
MLA	Fang, Zheyan,et al."GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases".INNOVATION 5.2(2024).