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- Title
Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates vascular endothelial growth factor expression.
- Authors
Sato, Fuyuki; Bhawal, Ujjal Kumar; Kawamoto, Takeshi; Fujimoto, Katsumi; Imaizumi, Tadaatsu; Imanaka, Tadanobu; Kondo, Jun; Koyanagi, Satoru; Noshiro, Mitsuhide; Yoshida, Hidemi; Kusumi, Tomomi; Kato, Yukio; Kijima, Hiroshi
- Abstract
DEC1 (BHLHB2/Sharp2/Stra13) and DEC2 (BHLHB3/Sharp1) are basic-helix-loop-helix (bHLH) transcription factors, involved in cellular differentiation, responses to hypoxia and circadian rhythms. We recently showed that the expression of DEC1 and DEC2 was up-regulated by hypoxia; however, the functions of these two factors under hypoxic conditions have not been elucidated in detail. It is well established that the expression of vascular endothelial growth factor (VEGF) is up-regulated by hypoxia, and the expression of VEGF in response to hypoxia depends on transcriptional activation by a heterodimer comprising hypoxia-inducible factor 1α (HIF-1α) and arylhydrocarbon receptor nuclear translocator 1 (ARNT1). In the present study, we showed that DEC2, but not DEC1, suppressed VEGF gene expression under hypoxic conditions. DEC2 protein was co-immunoprecipitated with HIF-1α but not with ARNT1. The binding of HIF-1α to the hypoxia response element (HRE) in the VEGF promoter was decreased by DEC2 over-expression, and increased by DEC2 knockdown. We also showed that the circadian expression of VEGF showed a reciprocal pattern to that of DEC2 in cartilage. DEC2 had a circadian oscillation in implanted Sarcoma 180 cells. We conclude that DEC2 negatively regulates VEGF expression and plays an important role in the pathological conditions in which VEGF is involved.
- Subjects
GENE expression; GROWTH factors; HYPOXEMIA; VASCULAR endothelial growth factors; GENETIC regulation; CYTOKINES
- Publication
Genes to Cells, 2008, Vol 13, Issue 2, p131
- ISSN
1356-9597
- Publication type
Article
- DOI
10.1111/j.1365-2443.2007.01153.x