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

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 vi tro and biochemical studies have demonstrated that tissue-specific expressi on of the mouse renin gene is regulated by the specific interaction between negative regulatory element (NRE) in the 5'-flanking region of the renin g ene and NRE binding protein (NREB). In this study, we examined the hypothes is 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 ge ne expression in this tissue in vivo. We used in vivo transfection of NRE t ranscription factor decoy (TFD) double-stranded oligonucleotide into the ra t liver via portal vein infusion. A gel mobility shift assay showed that tr ansfected NRE TFD blocked endogenous NREB binding with the rat renin gene. This resulted in enhanced hepatic renin mRNA expression, immunohistochemica l detection of renin in the liver, and consequently, increased plasma renin concentration. Taken together, these results document the importance of NR EB in the inhibition of renin gene expression in rat liver in vivo and sugg est the possibility of in vivo renin gene modulation by the TFD approach.