KLF2 Is a Novel Transcriptional Regulator of Endothelial Proinflammatory Activation

By S. Senbanerjee, Zhiyong Lin, G. Atkins, Daniel M. Greif, R. Rao, Ajay Kumar, M. W. Feinberg, Zhiping Chen, D. Simon, F. Luscinskas and 4 more. Journal of Experimental Medicine, 2004

737 citations recorded by the source corpus.

The vascular endothelium is a critical regulator of vascular function. Diverse stimuli such as proinflammatory cytokines and hemodynamic forces modulate endothelial phenotype and thereby impact on the development of vascular disease states. Therefore, identification of the regulatory factors that mediate the effects of these stimuli on endothelial function is of considerable interest. Transcriptional profiling studies identified the Kruppel-like factor (KLF)2 as being inhibited by the inflammatory cytokine interleukin-1β and induced by laminar shear stress in cultured human umbilical vein endothelial cells. Overexpression of KLF2 in umbilical vein endothelial cells robustly induced endothelial nitric oxide synthase expression and total enzymatic activity. In addition, KLF2 overexpression potently inhibited the induction of vascular cell adhesion molecule-1 and endothelial adhesion molecule E-selectin in response to various proinflammatory cytokines. Consistent with these observations, in vitro flow assays demonstrate that T cell attachment and rolling are markedly attenuated in endothelial monolayers transduced with KLF2. Finally, our studies implicate recruitment by KLF2 of the transcriptional coactivator cyclic AMP response element–binding protein (CBP/p300) as a unifying mechanism for these various effects. These data implicate KLF2 as a novel regulator of endothelial activation in response to proinflammatory stimuli.

Subfields: Genetics, Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cbe69f28d3f5e4002d821dbecc766be1a4bdb71a

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In Genetics

1. Klaus H. Kaestner
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Citations in the corpus

• Vascular Endothelial Cell Biology: An Update (2019, background): “The transcription factor KLF2 (Kruppel like factor 2) [54], which suppress an inflammatory activation, a feature missing in atherosclerosis-prone areas and characterized by a disturbed blood flow [55–58], is induced by arterial shear forces.”
• Mammalian Krüppel-Like Factors in Health and Diseases (2010, background): “KLFs regulate inflammatory responses in both endothelial and SMCs (172, 233, 369).”
• Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies (2021, background): “…as a novel therapeutic strategy to reverse endothelial dysfunction Activation of KLF2 and Kruppel-like factor 4 (KLF4) (master regulators of vascular homeostasis) inhibits inflammation in endothelial cells in response to proinflammatory cytokines (SenBanerjee et al., 2004; Hamik et al., 2007).”
• Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms (2005, neutral): “fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=5054">PAI1 )”
• Krüppel-like factor 4 regulates macrophage polarization. (2011, background): “The expression of KLF2, a closely related family member (38, 39), was unchanged (Figure 6A).”