期刊
BLOOD
卷 115, 期 12, 页码 2533-2542出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-06-228726
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资金
- Netherlands Heart Foundation [NHS93.007, 2008B105, 2003T032]
- Netherlands Organization for Scientific Research, The Hague, the Netherlands [050-110-1014]
- Hague
- European Union [LSHM-CT-2003-503254]
The shear stress-induced transcription factor Kruppel-like factor 2 (KLF2) confers antiinflammatory properties to endothelial cells through the inhibition of activator protein 1, presumably by interfering with mitogen-activated protein kinase (MAPK) cascades. To gain insight into the regulation of these cascades by KLF2, we used antibody arrays in combination with time-course mRNA microarray analysis. No gross changes in MAPKs were detected; rather, phosphorylation of actin cytoskeleton-associated proteins, including focal adhesion kinase, was markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated inhibition of Jun NH2-terminal kinase (JNK) and its downstream targetsATF2/c-Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of typical short basal actin filaments, termed shear fibers by us, which are distinct from thrombinor tumor necrosis factor-alpha-induced stress fibers. KLF2 is shown to be essential for shear stress-induced cell alignment, concomitant shear fiber assembly, and inhibition of JNK signaling. These findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers. (Blood. 2010; 115: 2533-2542)
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