Suppression of NF‐κB‐dependent gene expression by a hexamethylene bisacetamide‐inducible protein HEXIM1 in human vascular smooth muscle cells

Abstract

Background : Neointima formation is a characteristic feature of atherosclerosis and post-angioplasty restenosis, in which various soluble factors and mechanical injury stimulate signalling pathways in vascular smooth muscle cells (VSMC), promoting their migration and proliferation, and the eventual formation of the neointima. The transcription factor NF-κ κ κ κ B has been

Andrographolide inhibits NF-κB activation and attenuates neointimal hyperplasia in arterial restenosis

“…Consistent with previous findings [5,8,[25][26][27][28][29] in which the activation of NF-κB transcription factors, especially p50, is critical to neointimal hyperplasia, we have found that treatment with Andro and p50 ablation both significantly reduce neointimal formation without affecting medial thickening, attesting to the significance of NF-κB activation in the pathogenesis of arterial restenosis. Importantly, these experimental findings in mice are supported by the expression profiles of E-selectin, VCAM-1 and TF in samples of human thrombotic vasculitis.…”

The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1

“…The cells were then subjected to immunostaining using the anti-FLAG antibody. We observed nuclear localization of FLAG-EDG1 full-length (as previously reported in Ouchida et al, 2003) and the C-terminus FLAG-EDG1 (1-280) deletion mutant ( Figure 3a). The other C-terminus FLAG-EDG1 (1-310) deletion mutant and the two N-terminus deletion mutants also showed nuclear localization (data not shown).…”

“…Therefore, the inability of the C-terminus deletion FLAG-EDG1 mutants to repress transcription cannot be attributed to nonnuclear localization. Although the majority of the cells expressing the FLAG-EDG1 (D150-177) NLS deletion mutant showed non-nuclear localization as expected (Figure 3a), some of the cells showed nuclear localization of the FLAG-EDG1 (D150-177) NLS deletion mutant (data not shown and as reported in Ouchida et al, 2003). This may explain why minor repression by the FLAG-EDG1 (D150-177) NLS deletion mutant was observed in reporter assays (Figure 2c).…”

“…This may explain why minor repression by the FLAG-EDG1 (D150-177) NLS deletion mutant was observed in reporter assays (Figure 2c). Although previous studies have strongly implicated the EDG1 NLS region in nuclear localization (Michels et al, 2003;Ouchida et al, 2003), our data suggest that unknown factors, in Figure 3 Subcellular localization of EDG1 and EDG1 deletion mutants and their interaction with the E/F domain of ERa in vitro. (a) CHO cells were transfected with expression vectors for FLAG-EDG1 or FLAG-EDG1 deletion mutants and subjected to immunostaining as described in 'Materials and methods'.…”

“…EDG1/ HEXIM1 is also homologous to the mouse protein, cardiac lineage protein 1 (CLP-1), which has been implicated as a cell-specific transcriptional mediator of the cardiac MLC-2u promoter (Huang et al, 2002). Another study suggested that EDG1/HEXIM1 functions as a repressor of NF-kB-mediated transcription (Ouchida et al, 2003). For the rest of the manuscript, the term EDG1 will be used in place of EDG1/ HEXIM1, unless we are referring to work previously performed on HEXIM1.…”