Open AccessPAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells
Author(s) -
Shouqin Zhang,
Yingjie Yin,
Congye Li,
Yi Zhao,
Xinbo Wang,
Xiangyu Zhang
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.103173
Subject(s) - umbilical vein , tumor necrosis factor alpha , downregulation and upregulation , apoptosis , cytokine , microbiology and biotechnology , chemistry , endothelial stem cell , biology , immunology , biochemistry , in vitro , gene
Tumor necrosis factor-α (TNF) is a pro-inflammatory cytokine upregulated in many inflammatory diseases, and a potent inducer of endothelial cell-derived microparticle (EMP) formation. In this study, we identified the protein kinase PAK4 as a key regulator of the TNF-induced EMP release from human umbilical vein endothelial cells (HUVECs). TNF induces dose- and time-dependent EMP release and downregulation of PAK4 and upstream cdc42 in HUVECs. PAK4 suppression or inhibition of its kinase activity increases TNF-induced EMP release and apoptosis in HUVECs, while PAK4 overexpression reduces EMP release and apoptosis in TNF-stimulated cells. Collectively, these data indicate that PAK4 suppresses TNF-induced EMP generation occurring during apoptosis, and suggest that modulation of PAK4 activity may represent a novel approach to suppress the TNF-induced EMP levels in pro-inflammatory disorders and other pathological conditions.