title: A20 deficiency leads to angiogenesis of pulmonary artery endothelial cells through stronger NF-κB activation under hypoxia.
abstract: A20 is a zinc finger protein associated with hypoxia. As chronic hypoxia is responsible for intimal hyperplasia and disordered angiogenesis of pulmonary artery, which are histological hallmarks of pulmonary artery hypertension, we intended to explore the role of A20 in angiogenesis of pulmonary artery endothelial cells (ECs). Here, we found a transient elevation of A20 expression in the lung tissues from hypoxic rats compared with normoxic controls. This rapid enhancement was mainly detected in the endothelium, and similar results were reproduced in vitro. During early hypoxia, genetic inhibition of A20 increased proliferation in pulmonary artery ECs, linking to advanced cell cycle progression as well as microtubule polymerization, and aggravated angiogenic effects including tube formation, cell migration and adhesion molecules expression. In addition, a negative feedback loop between nuclear factor-kappa B and A20 was confirmed. Our findings provide evidence for an adaptive role of A20 against pulmonary artery ECs angiogenesis via nuclear factor-kappa B activation.
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.|Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.|Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.|Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.|Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.|Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Liuping
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.|Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Biopharmaceutical Sciences, Harbin Medical University, Daqing, Heilongjiang, China.|Department of Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002453:Cell Cycle; D015687:Cell Hypoxia; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D025461:Feedback, Physiological; D008297:Male; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011651:Pulmonary Artery / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; C000602677:TNFAIP3 protein, rat; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: A20; angiogenesis; hypoxia; nuclear factor-kappa B; pulmonary artery endothelial cells