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Updated: Jul 7, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates vascular endothelial growth factor
Fuyuki Sato1, Ujjal Kumar Bhawal, Takeshi Kawamoto
1Department of Pathology, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan. fsato@cc.hirosaki-u.ac.jp
Insights
DEC2, a transcription factor, suppresses vascular endothelial growth factor (VEGF) under hypoxia by interacting with HIF-1alpha. This finding is crucial for understanding VEGF
Area of Science:
- Molecular Biology
- Cellular Biology
- Gene Regulation
Background:
- DEC1 and DEC2 are bHLH transcription factors involved in cellular processes.
- Hypoxia up-regulates DEC1 and DEC2 expression, but their functions remain unclear.
- Vascular Endothelial Growth Factor (VEGF) expression is hypoxia-inducible via HIF-1alpha and ARNT1.
Purpose of the Study:
- To elucidate the functions of DEC1 and DEC2 under hypoxic conditions.
- To investigate the role of DEC2 in regulating VEGF gene expression.
- To determine the interaction between DEC2, HIF-1alpha, and VEGF regulation.
Main Methods:
- Co-immunoprecipitation assays to assess protein interactions.
- Analysis of VEGF promoter activity and HIF-1alpha binding under varying DEC2 expression levels.
- Investigation of circadian expression patterns of DEC2 and VEGF in cartilage and tumor cells.
Main Results:
- DEC2, but not DEC1, suppressed VEGF gene expression under hypoxia.
- DEC2 protein co-immunoprecipitated with HIF-1alpha, but not ARNT1.
- DEC2 overexpression decreased HIF-1alpha binding to the VEGF promoter's HRE, while knockdown increased it.
- Circadian expression of VEGF was inversely correlated with DEC2 in cartilage.
- DEC2 exhibited circadian oscillation in Sarcoma 180 cells.
Conclusions:
- DEC2 acts as a negative regulator of VEGF expression.
- DEC2 plays a significant role in pathological conditions involving VEGF.
- The interaction between DEC2 and HIF-1alpha is critical for controlling VEGF levels during hypoxia.
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 1alpha (HIF-1alpha) 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-1alpha but not with ARNT1. The binding of HIF-1alpha 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.
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