Transcription factor decoy to study the molecular mechanism of negative regulation of renin gene expression in the liver in vivo

被引:33
作者
Tomita, S
Tomita, N
Yamada, T
Zhang, LN
Kaneda, Y
Morishita, R
Ogihara, T
Dzau, VJ
Horiuchi, M
机构
[1] Osaka Univ, Sch Med, Dept Geriatr Med, Suita, Osaka 5650871, Japan
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA
[3] Osaka Univ, Sch Med, Dept Gene Therapy Sci, Suita, Osaka 565, Japan
[4] Ehime Univ, Sch Med, Dept Biochem Med, Matsuyama, Ehime 790, Japan
关键词
renin; negative regulatory element; transcription factor decoy; hemagglutinating virus of Japan liposome; gene expression;
D O I
10.1161/01.RES.84.9.1059
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Renin is synthesized in high quantities in the juxtaglomerular cells of the kidney, but little or none is synthesized in the liver. Our previous in vitro and biochemical studies have demonstrated that tissue-specific expression of the mouse renin gene is regulated by the specific interaction between negative regulatory element (NRE) in the 5'-flanking region of the renin gene and NRE binding protein (NREB). In this study, we examined the hypothesis that this interaction between the NRE in the promoter region of the rat renin gene and the NREB in the liver contributes to the suppressed renin gene expression in this tissue in vivo. We used in vivo transfection of NRE transcription factor decoy (TFD) double-stranded oligonucleotide into the rat liver via portal vein infusion. A gel mobility shift assay showed that transfected NRE TFD blocked endogenous NREB binding with the rat renin gene. This resulted in enhanced hepatic renin mRNA expression, immunohistochemical detection of renin in the liver, and consequently, increased plasma renin concentration. Taken together, these results document the importance of NREB in the inhibition of renin gene expression in rat liver in vivo and suggest the possibility of in vivo renin gene modulation by the TFD approach.
引用
收藏
页码:1059 / 1066
页数:8
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