論文

2007年11月

Thrombomodulin is a clock-controlled gene in vascular endothelial cells

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Norihiko Takeda
  • ,
  • Koji Maemura
  • ,
  • Shuichi Horie
  • ,
  • Katsutaka Oishi
  • ,
  • Yasushi Imai
  • ,
  • Tomohiro Harada
  • ,
  • Tetsuya Saito
  • ,
  • Taro Shiga
  • ,
  • Eisuke Amiya
  • ,
  • Ichiro Manabe
  • ,
  • Norio Ishida
  • ,
  • Ryozo Nagai

282
45
開始ページ
32561
終了ページ
32567
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M705692200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Cardiovascular diseases are closely related to circadian rhythm, which is under the control of an internal biological clock mechanism. Although a biological clock exists not only in the hypothalamus but also in each peripheral tissue, the biological relevance of the peripheral clock remains to be elucidated. In this study we searched for clock- controlled genes in vascular endothelial cells using microarray technology. The expression of a total of 229 genes was up- regulated by CLOCK/ BMAL2. Among the genes that we identified, we examined the thrombomodulin ( TM) gene further, because TM is an integral membrane glycoprotein that is expressed primarily in vascular endothelial cells and plays a major role in the regulation of intravascular coagulation. TM mRNA and protein expression showed a clear circadian oscillation in the mouse lung and heart. Reporter analyses, gel shift assays, and chromatin immunoprecipitation analyses using the TM promoter revealed that a heterodimer of CLOCK and BMAL2 binds directly to the E- box of the TM promoter, resulting in TM promoter transactivation. Indeed, the oscillation of TM gene expression was abolished in clock mutant mice, suggesting that TM expression is regulated by the clock gene in vivo. Finally, the phase of circadian oscillation of TM mRNA expression was altered by temporal feeding restriction, suggesting TM gene expression is regulated by the peripheral clock system. In conclusion, these data suggest that the peripheral clock in vascular endothelial cells regulates TM gene expression and that the oscillation of TM expression may contribute to the circadian variation of cardiovascular events.


リンク情報
DOI
https://doi.org/10.1074/jbc.M705692200
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000250625400005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M705692200
  • ISSN : 0021-9258
  • eISSN : 1083-351X
  • Web of Science ID : WOS:000250625400005

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