Thrombin-induced autoinhibitory factor, Down syndrome critical region-1, attenuates NFAT-dependent vascular cell adhesion molecule-1 expression and inflammation in the endothelium

The Journal of Biological Chemistry
T MinamiTatsuhiko Kodama

Abstract

Activation and dysfunction of the endothelium underlie many vascular disorders including atherosclerosis, tumor growth, and inflammation. We recently reported that thrombin and vascular endothelial growth factor, but not tumor necrosis factor-alpha, results in dramatic up-regulation of Down syndrome critical region (DSCR)-1 gene in endothelial cells, a negative feedback regulator of calcineurin-NFAT signaling. Constitutive expression of DSCR-1 in activated endothelial cells markedly impaired NFAT nuclear localization, proliferation, tube formation, and tumor growth. The goal of the present study was to elucidate the relative roles of NFAT/DSCR-1 and NF-kappaB/I-kappaB in mediating thrombin-responsive gene expression in endothelial cells. DNA microarrays of thrombin-treated human umbilical vein endothelial cells overexpressing DSCR-1 or constitutive active IkappaBalpha revealed genes that were dependent on NFAT and/or NF-kappaB activity. Vascular cell adhesion molecule-1 was inhibited both by DSCR-1 and I-kappaB at the level of mRNA, protein, promoter activity, and function (monocyte adhesion). Using a combination of transient transfections, electrophoretic mobility shift assays, and chromatin immunoprecipitation, thrombin was s...Continue Reading

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Citations

Aug 14, 2009·The Journal of Biological Chemistry·Haihua SongTakashi Minami
Oct 24, 2009·Journal of Vascular Research·Anthony Wayne OrrBrian R Wamhoff
Nov 22, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·A Wayne OrrBrian R Wamhoff
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Feb 2, 2012·Biochemical and Biophysical Research Communications·Seon Sook KimSu Ryeon Seo
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Aug 14, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Masashi MuramatsuTakashi Minami
Apr 2, 2021·Frontiers in Cardiovascular Medicine·Yaoyao CaiLihua Li
May 8, 2021·Gastroenterology Research and Practice·Jianxing ZhengXiaogang Liu
Aug 1, 2021·Biochemical and Biophysical Research Communications·Masashi MuramatsuTakashi Minami
Aug 20, 2021·Inflammation and Regeneration·Takahiro ManabeTakashi Minami

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