Open AccessAdiporedoxin suppresses endothelial activation via inhibiting MAPK and NF-κB signaling
Author(s) -
Hui He,
Fang Guo,
Yong Li,
Fatma Saaoud,
Brooks David Kimmis,
Jeena K. Sandhu,
Michelle Fan,
Dev Maulik,
Susan M. Lessner,
Christopher J. Papasian,
Daping Fan,
ZhiSheng Jiang,
Mingui Fu
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep38975
Subject(s) - umbilical vein , mapk/erk pathway , microbiology and biotechnology , signal transduction , chemistry , tumor necrosis factor alpha , gene knockdown , p38 mitogen activated protein kinases , nf κb , endothelial stem cell , vcam 1 , biology , cell adhesion molecule , endocrinology , biochemistry , icam 1 , apoptosis , in vitro
Adiporedoxin (Adrx) is a recently discovered redox regulatory protein that is preferentially expressed in adipose tissue and plays a critical role in the regulation of metabolism via its modulation of adipocyte protein secretion. We here report that Adrx suppresses endothelial cell activation via inhibiting MAPK and NF-kB signaling pathways. Adrx is constitutively expressed in human vascular endothelial cells, and significantly induced by a variety of stimuli such as TNFα, IL-1β, H 2 O 2 and OxLDL. Overexpression of Adrx significantly attenuated TNFα-induced expression of VCAM-1 and ICAM-1, and thus reduced monocyte adherence to human umbilical vein endothelial cells (HUVECs). Conversely, siRNA-mediated knockdown of Adrx increased TNFα-induced expression of adhesion molecules and monocyte adherence to HUVECs. Furthermore, forced expression of Adrx decreased TNFα-induced activation of ERK1/2, JNK, p38 and IKKs in HUVECs. Adrx mutant in the CXXC motif that lost its anti-redox activity is less efficient than the wild-type Adrx, suggesting that Adrx-mediated inhibition of endothelial activation is partially dependent on its antioxidant activity. Finally, Adrx expression was markedly increased in human atheroma compared with normal tissue from the same carotid arteries. These results suggest that Adrx is an endogenous inhibitor of endothelial activation, and might be a therapeutic target for vascular inflammatory diseases.