气候变化领域集成服务门户(CCPortal): MEKK3–TGFβ crosstalk regulates inward arterial remodeling

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DOI	10.1073/pnas.2112625118
	MEKK3–TGFβ crosstalk regulates inward arterial remodeling
	Deng H.; Xu Y.; Hu X.; Zhuang Z.W.; Chang Y.; Wang Y.; Ntokou A.; Schwartz M.A.; Su B.; Simons M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:51
英文摘要	Arterial remodeling is an important adaptive mechanism that maintains normal fluid shear stress in a variety of physiologic and pathologic conditions. Inward remodeling, a process that leads to reduction in arterial diameter, plays a critical role in progression of such common diseases as hypertension and atherosclerosis. Yet, despite its pathogenic importance, molecular mechanisms controlling inward remodeling remain undefined. Mitogen-activated protein kinases (MAPKs) perform a number of functions ranging from control of proliferation to migration and cell-fate transitions. While the MAPK ERK1/2 signaling pathway has been extensively examined in the endothelium, less is known about the role of the MEKK3/ERK5 pathway in vascular remodeling. To better define the role played by this signaling cascade, we studied the effect of endothelial-specific deletion of its key upstream MAP3K, MEKK3, in adult mice. The gene’s deletion resulted in a gradual inward remodeling of both pulmonary and systematic arteries, leading to spontaneous hypertension in both vascular circuits and accelerated progression of atherosclerosis in hyperlipidemic mice. Molecular analysis revealed activation of TGFβ-signaling both in vitro and in vivo. Endothelial-specific TGFβR1 knockout prevented inward arterial remodeling in MEKK3 endothelial knockout mice. These data point to the unexpected participation of endothelial MEKK3 in regulation of TGFβR1-Smad2/3 signaling and inward arterial remodeling in artery diseases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Atherosclerosis; Inward arterial remodeling; MEKK3; Pulmonary arterial hypertension; Systemic hypertension
语种	英语
scopus关键词	Map3k3 protein, mouse; mitogen activated protein kinase kinase kinase 1; mitogen activated protein kinase kinase kinase 3; selective estrogen receptor modulator; tamoxifen; transforming growth factor beta; transforming growth factor beta receptor; animal; drug effect; gene deletion; gene expression regulation; genetics; genotype; hindlimb; human; ischemia; metabolism; mouse; pathology; physiology; pulmonary hypertension; signal transduction; umbilical vein endothelial cell; vascular remodeling; vascularization; Animals; Gene Deletion; Gene Expression Regulation; Genotype; Hindlimb; Human Umbilical Vein Endothelial Cells; Humans; Hypertension, Pulmonary; Ischemia; MAP Kinase Kinase Kinase 1; MAP Kinase Kinase Kinase 3; Mice; Receptors, Transforming Growth Factor beta; Selective Estrogen Receptor Modulators; Signal Transduction; Tamoxifen; Transforming Growth Factor beta; Vascular Remodeling
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250908
作者单位	Yale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511, United States; Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China; Department of Microbiology and Immunology, Ministry of Education Key Laboratory of Cell Death and Differentiation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06510, United States; Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06511, United States; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, United States
推荐引用方式 GB/T 7714	Deng H.,Xu Y.,Hu X.,等. MEKK3–TGFβ crosstalk regulates inward arterial remodeling[J],2021,118(51).
APA	Deng H..,Xu Y..,Hu X..,Zhuang Z.W..,Chang Y..,...&Simons M..(2021).MEKK3–TGFβ crosstalk regulates inward arterial remodeling.Proceedings of the National Academy of Sciences of the United States of America,118(51).
MLA	Deng H.,et al."MEKK3–TGFβ crosstalk regulates inward arterial remodeling".Proceedings of the National Academy of Sciences of the United States of America 118.51(2021).