A20 deficiency leads to angiogenesis of pulmonary artery endothelial cells through stronger NF‐κB activation under hypoxia. Issue 7 (17th March 2016)

• Record Type: Journal Article
• Authors: Li, Jing; Zhang, Linlin; Zhang, Yueming; Liu, Ying; Zhang, Hongyue; Wei, Liuping; Shen, Tingting; Jiang, Chun; Zhu, Daling
• Is Part Of: Journal of cellular and molecular medicine. Volume 20:Issue 7(2016)
• Page Start: 1319
• Page End: 1328
• Publication Date: 2016-03-17
• Subjects: A20 -- hypoxia -- angiogenesis -- pulmonary artery endothelial cells -- nuclear factor‐kappa B; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12816
• Languages: English
• ISSNs: 1582-1838

Abstract

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.