© 1999 American Heart Association, Inc.
Original Contributions |
Transcription Factor Decoy to Study the Molecular Mechanism of Negative Regulation of Renin Gene Expression in the Liver In Vivo
From the Division of Cardiovascular Medicine, Department of Medicine (S.T., N.T., T.Y., L.Z., V.J.D., M.H.), Brigham and Women's Hospital, Harvard University Medical School, Boston, Mass; Department of Geriatric Medicine (S.T., N.T., R.M., T.O.), Osaka University Medical School, Suita, Japan; Department of Gene Therapy Science (Y.K., R.M.), Osaka University Medical School, Suita, Japan; and Department of Medical Biochemistry (M.H.), Ehime University School of Medicine, Ehime, Japan.
Correspondence to Naruya Tomita, Department of Geriatric Medicine, Osaka University Medical School, 2-2 Yamada-oka, Suita 565-0871, Japan. E-mail tomita{at}geriat.med.osaka-u.ac.jp
Abstract—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.
Key Words: renin • negative regulatory element • transcription factor decoy • hemagglutinating virus of Japan liposome • gene expression
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