Kruppel-like factor 2 inhibits protease activated receptor-1 expression and thrombin-mediated endothelial activation

Arteriosclerosis, Thrombosis, and Vascular Biology
Zhiyong LinMukesh K Jain

Abstract

The serine protease thrombin can dramatically alter endothelial gene expression in a manner that confers a proinflammatory phenotype. Recent studies have identified the Kruppel-like factor 2 (KLF2) as a critical regulator of endothelial gene expression. Herein, we provide evidence that KLF2 inhibits thrombin-mediated endothelial activation via alterations in expression of its principal receptor protease-activated receptor-1 (PAR-1). Forced expression of KLF2 in human umbilical vein endothelial cells potently inhibited the ability of thrombin to induce multiple prothrombotic factors (tissue factor, CD40L, plasminogen activator inhibitor-1), cytokines/chemokines (eg, monocyte chemotactic protein-1, interleukin-6 [IL-6], IL-8), and matrix degrading enzymes (eg, matrix metalloproteinases 1, 2, and 9). Mechanistically, KLF2 inhibits PAR-1 expression and, as a consequence, thrombin-mediated nuclear factor kappaB (NF-kappaB) nuclear accumulation and DNA binding. Conversely, small interfering RNA-mediated knockdown of KLF2 increases PAR-1 expression and thrombin-mediated induction of NF-kappaB activation. These studies identify KLF2 as a novel regulator of PAR-1 expression and thrombin action in endothelial cells.

References

Jan 1, 1986·The Journal of Clinical Investigation·T D Gelehrter, R Sznycer-Laszuk
Sep 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·V MarinG Kaplanski
Oct 11, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Takashi MinamiWilliam C Aird
May 12, 2004·The Journal of Experimental Medicine·Sucharita SenBanerjeeMukesh K Jain
Sep 29, 2004·Trends in Cardiovascular Medicine·Mark W FeinbergMukesh K Jain
Feb 19, 2005·Circulation Research·Zhiyong LinMukesh K Jain
Jul 29, 2005·The American Journal of Pathology·Rob J DekkerAnton J G Horrevoets

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Citations

Nov 26, 2009·European Journal of Human Genetics : EJHG·Tiia Kangas-KontioMarkku J Savolainen
Jun 6, 2009·The Journal of Biological Chemistry·Daiji KawanamiMukesh K Jain
Oct 6, 2010·Antioxidants & Redox Signaling·Lalitha NayakMukesh K Jain
Dec 17, 2015·The Journal of Infectious Diseases·Soumya PanigrahiMichael M Lederman
Jan 1, 2015·Nature Reviews. Disease Primers·Alisa S WolbergNigel Mackman
Apr 30, 2016·Blood·Marvin T Nieman
Nov 24, 2016·Hämostaseologie·James R Byrnes, Alisa S Wolberg
Dec 23, 2016·Thrombosis and Haemostasis·Jie GaoDazhuo Shi
Jun 23, 2007·Circulation Research·G Brandon Atkins, Mukesh K Jain
Dec 30, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Reinier A BoonAnton J G Horrevoets
Nov 11, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Katsuya Hirano
Apr 22, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Wolfram Ruf
Jan 9, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Heiko MetheElazer R Edelman
May 30, 2019·Physiological Reviews·Nina WettschureckStefan Offermanns
Jul 28, 2019·Current Opinion in Hematology·Laurent O Mosnier
Dec 17, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Beibei JiangJincai Luo
Dec 21, 2010·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Paul R ClarkJordan S Pober
Mar 25, 2016·Journal of Intensive Care·Naoyuki Matsuda
Mar 7, 2007·The Journal of Biological Chemistry·Anne HamikMukesh K Jain
Feb 21, 2018·Frontiers in Cardiovascular Medicine·David R SweetMukesh K Jain
Jun 8, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Janine ZahltenStefan Hippenstiel
Jan 16, 2021·International Journal of Molecular Sciences·Andy W C ManNing Xia
Jun 5, 2021·American Journal of Respiratory Cell and Molecular Biology·Sadiya S Khan
Jul 27, 2011·Biochemical and Biophysical Research Communications·Daiji KawanamiKazunori Utsunomiya

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