Vascular Endothelial Growth Factor(VEGF) expression is negatively regulated by Basic-Helix-Loop-Helix (BHLH) transcription factor DEC2

Hiroshi Kijima, Fuyuki Sato, Ujjal Kumar Bhawal, Takeshi Kawamoto, Katsumi Fujimoto, Tadaatsu Imaizumi, Tadanobu Imanaka, Jun Kondo, Koyanagi Satoru, Mitsuhide Noshiro, Hidemi Yoshida, Yukio Kato

Research output: Contribution to journalArticle

Abstract

The circadian rhythms in mammals are regulated by a pacemaker located in the suprachiasmatic nucleus of the hypothalamus. Five clock-gene families, i.e. Clock, Bmal, Per, Cry and Dec, have been found to be involved in a transcription-translation feedback loop that generates the circadian rhythm at the intracellular level. In this study, we examined functional analysis of the Dec gene. DEC1 and DEC2 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 upregulated 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 upregulated by hypoxia, and the expression of VEGF in response to hypoxia depends on transcriptional activation by a heterodimer comprising hypoxia-inducible factor 1 a (HIF-la) 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-1 a but not with ARNT1. The binding of HIF-la to the hypoxia response element (HRE) in the VEGF promoter was decreased by DEC2 overexpression, 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.

Original languageEnglish
JournalHirosaki Medical Journal
Volume61
Issue numberSUPPL.
Publication statusPublished - Jul 8 2010

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Basic Helix-Loop-Helix Transcription Factors
Vascular Endothelial Growth Factor A
Circadian Rhythm
Cytoplasmic and Nuclear Receptors
Sarcoma 180
Hypoxia-Inducible Factor 1
Suprachiasmatic Nucleus
Response Elements
Transcriptional Activation
Genes
Hypothalamus
Cartilage
Mammals
Hypoxia
Gene Expression

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Kijima, H., Sato, F., Bhawal, U. K., Kawamoto, T., Fujimoto, K., Imaizumi, T., ... Kato, Y. (2010). Vascular Endothelial Growth Factor(VEGF) expression is negatively regulated by Basic-Helix-Loop-Helix (BHLH) transcription factor DEC2. Hirosaki Medical Journal, 61(SUPPL.).

Vascular Endothelial Growth Factor(VEGF) expression is negatively regulated by Basic-Helix-Loop-Helix (BHLH) transcription factor DEC2. / Kijima, Hiroshi; Sato, Fuyuki; Bhawal, Ujjal Kumar; Kawamoto, Takeshi; Fujimoto, Katsumi; Imaizumi, Tadaatsu; Imanaka, Tadanobu; Kondo, Jun; Satoru, Koyanagi; Noshiro, Mitsuhide; Yoshida, Hidemi; Kato, Yukio.

In: Hirosaki Medical Journal, Vol. 61, No. SUPPL., 08.07.2010.

Research output: Contribution to journalArticle

Kijima, H, Sato, F, Bhawal, UK, Kawamoto, T, Fujimoto, K, Imaizumi, T, Imanaka, T, Kondo, J, Satoru, K, Noshiro, M, Yoshida, H & Kato, Y 2010, 'Vascular Endothelial Growth Factor(VEGF) expression is negatively regulated by Basic-Helix-Loop-Helix (BHLH) transcription factor DEC2', Hirosaki Medical Journal, vol. 61, no. SUPPL..
Kijima, Hiroshi ; Sato, Fuyuki ; Bhawal, Ujjal Kumar ; Kawamoto, Takeshi ; Fujimoto, Katsumi ; Imaizumi, Tadaatsu ; Imanaka, Tadanobu ; Kondo, Jun ; Satoru, Koyanagi ; Noshiro, Mitsuhide ; Yoshida, Hidemi ; Kato, Yukio. / Vascular Endothelial Growth Factor(VEGF) expression is negatively regulated by Basic-Helix-Loop-Helix (BHLH) transcription factor DEC2. In: Hirosaki Medical Journal. 2010 ; Vol. 61, No. SUPPL.
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AU - Kijima, Hiroshi

AU - Sato, Fuyuki

AU - Bhawal, Ujjal Kumar

AU - Kawamoto, Takeshi

AU - Fujimoto, Katsumi

AU - Imaizumi, Tadaatsu

AU - Imanaka, Tadanobu

AU - Kondo, Jun

AU - Satoru, Koyanagi

AU - Noshiro, Mitsuhide

AU - Yoshida, Hidemi

AU - Kato, Yukio

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