Details

Autor(en) / Beteiligte

• Zhang, Shouqin
• Yin, Yingjie
• Li, Congye
• Zhao, Yi
• Wang, Qixing
• Zhang, Xiangyu

Titel

PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells

Ist Teil von

• Aging (Albany, NY.), 2020-07, Vol.12 (13), p.12740-12749

Ort / Verlag

United States: Impact Journals

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.