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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Tomita, S; Tomita, N; Yamada, T; Zhang, L; Kaneda, Y; Morishita, R; Ogihara, T; Dzau, VJ; Horiuchi, M

Published Date

  • May 14, 1999

Published In

Volume / Issue

  • 84 / 9

Start / End Page

  • 1059 - 1066

PubMed ID

  • 10325243

International Standard Serial Number (ISSN)

  • 0009-7330

Language

  • eng

Conference Location

  • United States