SREBP inhibits VEGF expression in human smooth muscle cells
- Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka (Japan)
- Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki (Japan)
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo (Japan)
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate expression of genes encoding enzymes for lipid biosynthesis. SREBPs are activated by HMG-CoA reductase inhibitors (statins). Statins have been also reported to suppress vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMCs). Therefore, we hypothesized that SREBPs are involved in statin-mediated regulation of VEGF production in VSMCs. SREBP1 was robustly expressed, and was activated by atorvastatin in VSMCs, as demonstrated by increased levels of the mature nuclear form of SREBP1, and increased promoter activities of a reporter containing sterol regulatory elements by atorvastatin. Moreover, overexpression of SREBP1a dose-dependently suppressed VEGF promoter activity. Site-specific mutation or deletion of the proximal Sp1 sites reduced the inhibitory effects of SREBP1a on VEGF promoter activity. These data demonstrated that SREBP1, activated by atorvastatin, suppressed VEGF expression through the indirect interaction with the proximal tandem Sp1 sites in VSMCs.
- OSTI ID:
- 20798878
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 342, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.01.139; PII: S0006-291X(06)00235-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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