Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 391, Issue 1, Pages 984-989Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.12.002
Keywords
Endothelial cells; KLF4; MEK5; KLF2; Shear stress; Resveratrol
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Funding
- National Institutes of Health [HL-076686, HL-090856]
- Howard Hughes Medical Institute Research
- American Federation for Aging Research/National Institute on Aging [T35 AG026781]
- Department of Innovation, Universities and Enterprise, Government of Catalonia, Spain
- Spanish Association
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL090856, R01HL076686] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [T35AG026781] Funding Source: NIH RePORTER
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The Kruppel-like factor 2 (KLF2) and Kruppel-like factor 4 (KLF4) transcription factors have recently been shown to act as critical regulators of endothelial homeostasis. While several insights have been made into the signaling mechanisms orchestrating endothelial KLF2 expression, those governing the expression of KLF4 in the vascular endothelium remain largely unknown. Here, we show that diverse vasoprotective stimuli including all atheroprotective shear stress waveform, simvastatin, and resveratrol induce the expression of KLF4 in cultured human endothelial cells We further demonstrate that the induction of KLF4 by resveratrol and atheroprotective shear stress occurs via a MEK5/MEF2-dependent signaling pathway. Since MEK5 activation is also critical for the expression of KLF2, we assessed the individual contribution of KLF4 and KLF2 to the global transcriptional activity triggered by MEK5 activation. Genome-wide transcriptional profiling of endothelial cells overexpressing KLF4, KLF2, or constitutively active MEK5 revealed that 59.2% of the genes regulated by the activation of MEK5 were similarly controlled by either KLF2 or KLF4 Collectively, Our data identify a significant degree of mechanistic and functional conservation between KLF2 and KLF4, and importantly, provide further insights into the complex regulatory networks governing endothelial vasoprotection. (C) 2009 Elsevier Inc. All rights reserved.
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