MISC

2009年4月

Transcription Factor Activating Protein-2 beta: A Positive Regulator of Monocyte Chemoattractant Protein-1 Gene Expression

ENDOCRINOLOGY
  • Motoyuki Kondo
  • ,
  • Hiroshi Maegawa
  • ,
  • Toshiyuki Obata
  • ,
  • Satoshi Ugi
  • ,
  • Kazuhiro Ikeda
  • ,
  • Katsutaro Morino
  • ,
  • Yukie Nakai
  • ,
  • Yoshihiko Nishio
  • ,
  • Shiro Maeda
  • ,
  • Atsunori Kashiwagi

150
4
開始ページ
1654
終了ページ
1661
記述言語
英語
掲載種別
DOI
10.1210/en.2008-1361
出版者・発行元
ENDOCRINE SOC

We previously reported an association between the activating protein (AP)-2 beta transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with a disease-susceptible allele of AP-2 beta showed stronger AP-2 beta expression in adipose tissue than those without the susceptible allele. Furthermore, overexpression of AP-2 beta leads to lipid accumulation by enhancing glucose transport and inducing insulin resistance in 3T3-L1 adipocytes. In this study, we found that overexpression of AP-2 beta in 3T3-L1 adipocytes accelerated the promoter activity of monocyte chemoattractant protein-1 (MCP-1) and subsequently increased both mRNA and protein expression and protein secretion. Furthermore, knockdown of endogenous AP-2 beta by RNA interference reduced the mRNA and the protein expression of MCP-1. EMSAs and chromatin immunoprecipitation assays revealed specific binding of AP-2 beta to MCP-1 promoter regions, in vitro and in vivo. Additionally, site-directed mutagenesis of the AP-2 binding site located at-137 to-129 relative to the transcription start site markedly diminished MCP-1 promoter activity, whereas other putative AP-2 binding sites did not. Our results clearly show that AP-2 beta directly enhanced MCP-1 secretion by binding to its promoter. Thus, we propose that AP-2 beta positively regulates MCP-1 expression; subsequently contributes to the infiltration of macrophages to adipose tissue; and leads to insulin resistance, type 2 diabetes, and cardiovascular diseases. (Endocrinology 150: 1654-1661, 2009)

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1210/en.2008-1361
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000264442900013&DestApp=WOS_CPL

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