＜Symposium I＞Vascular endothelial growth factor（ VEGF） expression is negatively regulated by basic-helix-loop-helix（ bHLH）transcription factor DEC2

フォーマット:

論文

責任表示:

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

言語:

英語

出版情報:

弘前大学大学院医学研究科・弘前医学会, 2010-07-08

著者名:

Kijima, Hiroshi

Sato, Fuyuki

Bhawal, Ujjal Kumar

Kawamoto, Takeshi

Fujimoto, Katsumi

Imaizumi, Tadaatsu

Imanaka, Tadanobu

Kondo, Jun

Koyanagi, Satoru

Noshiro, Mitsuhide

Yoshida, Hidemi

Kato, Yukio

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掲載情報:

弘前医学

ISSN:

0439-1721      

巻:

61

通号:

Supplement

開始ページ:

S43

終了ページ:

S52

バージョン:

publisher

概要:

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-transl … ation 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 diff erentiation, 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 α （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 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. 続きを見る

URL:

http://hdl.handle.net/10129/3669