Open AccessA20 deficiency leads to angiogenesis of pulmonary artery endothelial cells through stronger NF ‐κB activation under hypoxia
Author(s) -
Li Jing,
Zhang Linlin,
Zhang Yueming,
Liu Ying,
Zhang Hongyue,
Wei Liuping,
Shen Tingting,
Jiang Chun,
Zhu Daling
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12816
Subject(s) - angiogenesis , hypoxia (environmental) , pulmonary artery , endothelium , pulmonary hypertension , endothelial stem cell , hyperplasia , biology , cancer research , pathology , medicine , in vitro , chemistry , biochemistry , organic chemistry , oxygen
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 ( EC s). 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 EC s, 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 EC s angiogenesis via nuclear factor‐kappa B activation.