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 language | English |
|---|---|
| Journal | Hirosaki Medical Journal |
| Volume | 61 |
| Issue number | SUPPL. |
| Publication status | Published - Jul 8 2010 |
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All Science Journal Classification (ASJC) codes
- Medicine(all)
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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 journal › Article
}
TY - JOUR
T1 - Vascular Endothelial Growth Factor(VEGF) expression is negatively regulated by Basic-Helix-Loop-Helix (BHLH) transcription factor DEC2
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
PY - 2010/7/8
Y1 - 2010/7/8
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:77955879227
VL - 61
JO - Hirosaki Medical Journal
JF - Hirosaki Medical Journal
SN - 0439-1721
IS - SUPPL.
ER -