Communicated by: Shunsuke Ishii
Suppression of NF-κB-dependent gene expression by a hexamethylene bisacetamide-inducible protein HEXIM1 in human vascular smooth muscle cells
Article first published online: 12 FEB 2003
Genes to Cells
Volume 8, Issue 2, pages 95–107, February 2003
How to Cite
Ouchida, R., Kusuhara, M., Shimizu, N., Hisada, T., Makino, Y., Morimoto, C., Handa, H., Ohsuzu, F. and Tanaka, H. (2003), Suppression of NF-κB-dependent gene expression by a hexamethylene bisacetamide-inducible protein HEXIM1 in human vascular smooth muscle cells. Genes to Cells, 8: 95–107. doi: 10.1046/j.1365-2443.2003.00618.x
- Issue published online: 12 FEB 2003
- Article first published online: 12 FEB 2003
- Received: 12 October 2002 Accepted: 5 November 2002
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-κB has been shown to play a pivotal role in this process. Hexamethylene bisacetamide, an inhibitor of VSMC proliferation, induces the mRNA expression of HEXIM1 (hexamethylene bisacetamide-inducible protein 1). However, the protein expression and function of HEXIM1 remain unknown.
Results: In the present study, we demonstrated that HEXIM1 localizes in the cytoplasm and nucleus, and its nuclear expression is restricted to discrete speckled areas. Treatment of VSMC with hexamethylene bisacetamide up-regulated HEXIM1 expression, not only in mRNA but also protein levels. Moreover, HEXIM1 is shown to suppress the transcriptional activity of NF-κB via its C-terminal leucine-rich domain. A glutathione-S-transferase pull down assay indicated that HEXIM1 interacts with the p65 subunit of NF-κB. In VSMC, treatment with hexamethylene bisacetamide resulted in a down-modulation of the transcription of NF-κB target genes.
Conclusion: We may therefore conclude that HEXIM1 plays an inhibitory role in NF-κB-dependent gene expression in VSMC and is the candidate of a novel therapeutic target for inhibition of VSMC proliferation.